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Formation of Physical Hydrogels via Host−Guest Interactions of β-Cyclodextrin Polymers and Copolymers Bearing Adamantyl Groups
Abstract
In this paper, we would like to present a novel system of host−guest hydrogels. By polymerizing adamantyl containing acrylamide monomers (12−15) with water soluble comonomers, we synthesized various copolymers bearing guest components. As host system we applied easily accessible β-cyclodextrin polymers with Mn values of about 30K−100K g mol−1. The viscosity of the resulting hydrogel could be influenced by the concentration of both substances, by the length of the carbon spacer chain of the guest monomer, by the pH value or by the conformation of the β-cyclodextrin polymers. Moreover, the hydrogels stayed stable in solutions of starch hydrolyzing enzyme taka-diastase from Aspergillus oryzae.
... Therefore, the polymerization of β-CD could overcome such a problem, since it was transformed from crystalline to an amorphous one of higher solubility [16]. Recently, stable supramolecular hydrogels were formed from the hydrophobic interactions between CD-derived polymers and hydrophobic guest molecule end-capping polymers, such as hydrophobically modified dextran [13][14][15], hydrophobically modified polyacrylamide copolymer [17], and high-molecular-weight polyethylene glycols (PEG)s [18], which are used in controlled drug delivery applications. ...
... A native anhydrous β-CD was polymerized according to the previously reported method [17], into a soluble pβ-CD using EP as a crosslinking agent in an alkaline medium. Briefly, a native β-CD (10 g, 8.82 mmol) has been dissolved in 15 mL NaOH solution (15% w/v) and allowed to be stirred at 35 • C for 2 h. ...
... Toluene (2 mL) was added to the above alkaline solution and was stirred at the same temperature for a further 2 h. After, a calculated amount of EP (4.62 g, 50 mmol) [17] was added to that mixture and allowed to be stirred for 3 h. Then, the crude product was collected via precipitation of the solution mixture in 200 mL isopropanol solvent. ...
An inclusion complexation, between polymerized β-cyclodextrin and cholesterol end-capping branched polyethylene glycol, was utilized for constructing a self-assembled hydrogel. The physicochemical properties, the in vitro release profiles of 5-Fluorouracil/methotrexate (anticancer drugs), and the surface morphology of the resulting hydrogel were studied. Moreover, in vivo studies were carried out on female rats bearing breast cancer. The results revealed that the prepared systems were white in color, rubbery, and homogenous. The in vitro release studies showed an efficient ability of the modified system for drug loading and release in a sustained release manner for 14 days. The surface morphology was spongy porous. Moreover, the tumors’ healing was indicated from the analysis of tumor volume, plasma tumor markers, and histopathological analysis, compared to the controlled rats. The pharmacokinetic parameters appeared significant differences (p < 0.05) in the Cmax and Tmax of the medicated hydrogel samples, as compared with sole or combined saline-injected samples. The whole AUC of each drug in the medicated hydrogel samples was five-fold more than the mixture administrated in PBS. In conclusion, the proposed work delivered a hydrogel system that has a convenient ability for localized sustained release of breast cancer management.
... Noteworth, high molecular weight pβ-CD will be available for the inclusion crosslinking with various hydrophobic guest molecules. Such a characteristic is critical in developing stable self-assembling hydrogels (11)(12)(13)(14)(15)(16)(17). There are several methods for β-CD polymerization. ...
... There are several methods for β-CD polymerization. For example, the polymerization by crosslinking of β-CD with epichlorohydrin as crosslinking agent under strongly alkaline medium was reported by Koopmann et al. (12). ...
... Epichlorohydrin (EP), a crosslinking agent, was utilized for the polymerization of β-CD in an alkaline medium using the procedure reported by Koopman et al. (12). The schematic representation is illustrated in Fig. 1B. ...
Topical formulation of non-steroidal anti-inflammatory drugs (NSAIDs) exhibits many advantages over the oral administration route, such as avoiding the direct effect on GIT and avoiding the poor oral bioavailability of such drugs. Our study aims to develop a new self-assembling construct based on the hydrophobic interaction between adamantane terminated poly (ethylene glycol) polymers and polymerized β-cyclodextrin. The viscous constructs were developed from direct mixing of host and guest polymer solutions, indicating spontaneous formation without cross-linkers. The modified system was evaluated by different analyses, including X-ray diffractometry, electron microscopy, isothermal titration calorimetry, and rheological analysis. Moreover, such a system’s ability for drug loading and release was investigated via the in vitro release of ketorolac tromethamine (KT) as a model of NSAIDs. Finally, the prepared formulas were applied on a rat paw edema model to prove the enhanced anti-inflammatory activities. The obtained results indicated that the modified constructs have a rubbery porous structure with an amorphous nature. Also, from rheological results, the modified system exhibited a viscous behavior with higher loss modulus (G″) compared with storage (G′). The inclusion complexation between cyclodextrin and adamantane moieties was proved by the recorded high binding constants with a 1:1 stoichiometric ratio. Furthermore, the results showed the successful KT incorporation into the modified system and quantitatively released through a semi-permeable membrane in a sustained fashion (over 24 h). Finally, the in vivo results of the medicated constructs showed a significant inhibition of the induced inflammation and swelling, indicating that the modified construct has a great utility for safe non-irritating topical delivery applications.
... Mimicking biological systems is of great interest to materials researchers. Hydrogels [1][2][3][4][5][6], three-dimensional structured polymer networks, have been popular in biomedical applications [7,8] for mimicking biological systems [9][10][11][12][13][14][15] due to their biocompatibility and high water content. ...
... Based on a previous report on αCD-Azo hydrogels, a photoresponsive polymeric actuator was designed using [2] rotaxane architectures prepared by a polycondensation reaction between pseudo [2]rotaxanes of Lys-αCD with Azo and poly(ethylene glycol) (PEG) derivatives (Fig. 8a) [150]. The bending movement of topologically cross-linked αCD-Azo hydrogels can be observed upon irradiation with UV light (Fig. 8b), and topologically cross-linked αCD-Azo hydrogels quickly bend toward the light source upon UV irradiation (Fig. 8c). ...
... Based on a previous report on αCD-Azo hydrogels, a photoresponsive polymeric actuator was designed using [2] rotaxane architectures prepared by a polycondensation reaction between pseudo [2]rotaxanes of Lys-αCD with Azo and poly(ethylene glycol) (PEG) derivatives (Fig. 8a) [150]. The bending movement of topologically cross-linked αCD-Azo hydrogels can be observed upon irradiation with UV light (Fig. 8b), and topologically cross-linked αCD-Azo hydrogels quickly bend toward the light source upon UV irradiation (Fig. 8c). ...
Biological systems involve the most complex materials in the world. Mimicking biological systems is not an easy task. Materials researchers are continuing to push themselves to prepare synthetic materials that can replicate biological systems. Hydrogels have attracted great interest from materials researchers for mimicking biological systems due to their biocompatibility. One approach to preparing hydrogels is using host–guest interactions. Host–guest interactions can be achieved by using cyclodextrins (CDs) as host units and suitable guest units. Hydrogels prepared based on host–guest interactions show several functionalities, such as self-healing ability, stimuli responsiveness, the ability to function as soft actuators for use in artificial muscles, and conductive responsiveness. These functions can be attributed to reversible bond formation between the CDs and guest units. Self-healing materials, which mimic the recovery of injured skin, can be achieved if the association constant between the CDs and guests is sufficiently high. Several specific guest units can also show external stimuli responsivity (redox, pH, temperature, and light) when paired with CDs, allowing them to mimic the responsiveness of the human body to external stimuli. Light-responsive hydrogels can be used to prepare soft actuators that can be employed as artificial muscles to mimic the sliding motion of human sarcomeres. Conductive hydrogels will be required to support the function of artificial muscles in the near future. This review summarizes the advancements made in biofunctional hydrogels based on host–guest interactions.
... certain conditions, can overcome such shortening. Therefore, several physical hydrogel systems have been constructed from the inclusion complexation between pβ-CD with different hydrophobic molecules and the capping of high-molecular-weight polymers [4][5][6]. ...
... Firstly, the polymerization of β-CD (pβ-CD) was carried out by using EP, as a crosslinking agent, in an alkaline medium and toluene according to a previously reported method [4]. The crude product was collected by precipitation from isopropanol, redissolved in distilled water, neutralized with diluted HCl, and then dialyzed against water for 6 days for further purification where fresh water was replenished every 24 h. ...
Breast cancer is the second most common cancer in women worldwide. Long-term treatment with conventional chemotherapy may result in severe systemic side effects. Therefore, the localized delivery of chemotherapy helps to overcome such a problem. In this article, self-assembling hydrogels were constructed via inclusion complexation between host β-cyclodextrin polymers (8armPEG20k-CD and pβ-CD) and the guest polymers 8-armed poly(ethylene glycol) capped either with cholesterol (8armPEG20k-chol) or adamantane (8armPEG20k-Ad) and were loaded with 5-fluorouracil (5-FU) and methotrexate (MTX). The prepared hydrogels were characterized by SEM and rheological behaviors. The in vitro release of 5-FU and MTX was studied. The cytotoxicity of our modified systems was investigated against breast tumor cells (MCF-7) using an MTT assay. Additionally, the histopathological changes in breast tissues were monitored before and after their intratumor injection. The results of rheological characterization indicated the viscoelastic behavior in all cases except for 8armPEG-Ad. In vitro release results showed a variable range of release profiles from 6 to 21 days, depending on the hydrogel composition. MTT findings indicated the inhibition ability of our systems against the viability of cancer cells depending on the kind and concentration of the hydrogel and the incubation period. Moreover, the results of histopathology showed the improvement of cancer manifestation (swelling and inflammation) after intratumor injection of loaded hydrogel systems. In conclusion, the obtained results indicated the applicability of the modified hydrogels as injectable vehicles for both loading and controlled release of anticancer therapies.
... On the other hand, various conjugation chemistries can be used to react CD-based derivatives with side chains polymers: amidation [28][29][30][31][32] and Huisgen-type cycloaddition involving alkyne-pendent polymers and azide modified CDs [33][34][35] are the most prevalent synthetic routes. Other widespread host-polymer matrices are the commercialized hyperbranched CDs-polymers that are prepared from CDs cross-linked with epichlorohydrin 36,37 . Despite its easy implementation, the latter method falls short in controlling the architecture of the targeted network as well as the aforementioned strategies. ...
... Despite its easy implementation, the latter method falls short in controlling the architecture of the targeted network as well as the aforementioned strategies. Simultaneously, some guest-polymers can be synthetised from adamantane [28][29][30]35,36,38 , azobenzene 23,25,37,[39][40][41] , naphthalene 20,21,31 or pyrene substituents 21,22 to cite only a few molecules known for being complexed by CDs ( Figure I.4.b). Thus, the cooperative binding of host-and guest polymers though numerous interaction points is promoted by the side chain molecular recognition process which is very related to the antigen-antibody complex or the secondary structure of DNA or proteins. ...
Our increasing dependence on lithium-ion batteries for daily energy storage applications calls for the enhancement of their performances. Research efforts, which have so far relied on increasing energy densities, have recently been focused on durability and sustainability. In this context, the inspiration of life sciences has placed great hope on supramolecular chemistry to equip batteries with some added smart functionalities, in order to address their inherent failures such as electrodes swelling and partial dissolution, hence enhancing their lifespan. This work aims to evaluate how relevant this new worldwide research interest is, by focusing on cyclodextrins (CDs), which are bio-sourced cage molecules that can give reversible supramolecular host-guest interactions. We first successfully exploit the selective host-guest interaction of CDs towards polysulfides to discriminate these soluble lithium-sulfur batteries intermediates by nanopore, with a single sulfur atom resolution. Not only this approach lays the ground to the design of powerful sensors for electrolytes, but it also confers weight to a new sulfur confinement strategy based on CD. Next, we apply this host-guest interaction at the macromolecular scale by synthetizing mechanically interlocked architectures to be used as Si anode binders. Prepared from CDs-based polyrotaxanes (PRs) cross-linked with poly(acrylic acid), the PR-PAA prototypes disclose new routes of accommodating Si volume changes. Finally, we identify the crucial structural parameters involved in the better cyclability of Si anodes and provide an optimized design for PR-PAA binders.
... β-Cyclodextrin (β-CD) was purchased from J&K Scientific (Beijing, China), and β-cyclodextrin polymer (β-CDP) was synthesized by adapting the published procedures. 36 Zhengzhou Baiji Biotechnology Co., Ltd. (Henan, China). ...
... 1 H NMR (β-CDP, DMSO-d 6 ): δ = 3.28−3.95 (m), 4.49 (br), 4.85 (br), 5.73 (br).Based on the host−guest interaction of β-CDPs and Ad-Ds, we prepared a library containing 82 types of SNPs by adjusting the compositions and proportions of Ad-Ds.36 The compositions ...
Antibodies are the most common affinity reagents for specific targets recognition. However, their applications are limited by high cost and low stability. Thus, seeking substitutes for antibodies is of great significance. In this work, we designed a library containing 82 self-assembled nanoparticles (SNPs) based on self-assembly of β-cyclodextrin polymers and adamantane derivatives, and then screened out 8 types of SNPs capable of suppressing the toxicity of melittin by using hemolytic activity neutralization assay. The affinities of the SNPs to melittin were demonstrated by using surface plasmon resonance (SPR). As evidenced by cytotoxicity experiments, SNPs could also suppress the toxicity of melittin to other cells. In addition, in order to verify the universality of our method, 11 types of SNPs capable of neutralizing another toxic peptide, phenolic soluble polypeptide (PSMα3) secreted by Staphylococcus aureus, were selected from the same SNP library. Our self-assembly based method for library preparation has the advantages of flexible design, mild experimental condition and simple operation, which is expected to seek artificial affinity reagents for more species.
... On this basis we hypothesized that the pre-incubation of the carbohydrate with IBU prior to the addition of the crosslinker DVS may pre-organize the systems in a manner that resembles the molecular imprinting technology. Being aware that it is unlikely that the cross-linking of polysaccharides generates cavities complementary in size and charge to small molecules such as IBU, we were encouraged by the fact that the cross-linking of cyclodextrin in the presence or absence of toluene yields different polymers, being mainly linear in the former case and globular in the latter [19]. ...
Water recycling and reuse are corner stones in the water management that may be compromised by the presence of pollutants. Among them, pharmaceuticals can overcome the standard water treatments and require sophisticated approaches to remove them. Sorption is an economically affordable alternative limited by the need of sorbents that exhibit sorption coefficient (Kd) higher than 500 L/kg to be useful in wastewater treatment plants (WWTPs). We report that th cross-linking of dextrin (Dx) with divinyl sulfone (DVS) in presence of 1 mmol or 5 mmol of ibuprofen (IBU) yields the insoluble polymers pDx1 and pDx5 with improved affinity for IBU, Kd higher than 600 L/kg for ciprofloxacin (CIP) and ofloxacin and an outstanding Kd higher than 4000 L/kg for erythromycin (ERY), when assayed against a cocktail of 6 drugs. The characterization of the polymers by XRPD, TGA and SEM reveals that both pDx1 and pDx5 share similar features, with an ERY Kd of 13 x 103 for pDx1 and 6.4 x 103 for pDx5. The facts that new affinities and improvements in Kd can be achieved by cross-linking Dx in presence of other molecules that promote a pre-organization, broaden the applications of DVS cross-linked polysaccharide as sustainable and eco-friendly sorbents.
... On this basis, we hypothesized that the pre-incubation of the carbohydrate with IBU prior to the addition of the cross-linker DVS could preorganize the systems in a manner that resembles the molecular imprinting technology. As it is unlikely that the cross-linking of polysaccharides will generate cavities complementary in size and charge to small molecules such as IBU, we were encouraged by the fact that the cross-linking of cyclodextrin in the presence or absence of toluene yields different polymers, being predominantly linear in the former case and globular in the latter [19]. ...
Water recycling and reuse are cornerstones of water management, which can be compromised by the presence of pollutants. Among these, pharmaceuticals can overcome standard water treatments and require sophisticated approaches to remove them. Sorption is an economically viable alternative limited by the need for sorbents with a sorption coefficient (Kd) higher than 500 L/kg. The cross-linking of dextrin (Dx) with divinyl sulfone (DVS) in the presence of 1 mmol or 5 mmol of ibuprofen (IBU) yields the insoluble polymers pDx1 and pDx5 with improved affinity for IBU and high selectivity towards erythromycin (ERY) and ERY Kd higher than 4 × 10 3 L/kg, when tested against a cocktail of six drugs. Characterization of the polymers shows that both pDx1 and pDx5 have similar properties, fast sorption kinetics, and ERY Kd of 13.3 × 10 3 for pDx1 and 6.4 × 10 3 for pDx5, representing 26.6 and 12.0 times the 500 L/kg threshold. The fact that new affinities and improvements in Kd can be achieved by cross-linking Dx in the presence of other molecules that promote pre-organization expands the applications of DVS cross-linked polysaccharides as sustainable, scalable, and environmentally friendly sorbents with a potential application in wastewater treatment plants (WTPs).
... Adamantane (ADA) is a polycyclic hydrocarbon with a cage symmetric structure and high stability. Its binding capacity to β-CD is strong, with a binding constant of approximately 1 × 10 5 L/mol in water [14,45]. Pu et al. [46] synthesized a novel copolymer using acrylamide, acrylic acid, 6-acrylamide-β-cyclodextrin (N-β-CD) and acrylamide-adamantane (N-ADA) by radical micelles. ...
... The drug is made more soluble by forming such a complex, released sustainably, and the efficacy is improved (Gandhi et al., 2020;Ramasamy et al., 2018b;Gidwani & Vyas, 2015). Cyclodextrin polymers have been synthesized to enhance the drug-carrying capacity (Pillai et al., 2022a;Koopmans & Ritter, 2008). We hypothesized that a novel combination of Dy-doped nickel sulfide nanoparticles with poly-β-cyclodextrin (poly-CD) would be an innovative combination for chemotherapy and photothermal treatment of breast cancer cells. ...
Newer materials for utilization in multi-directional therapeutic actions are investigated, considering delicate design principles involving size and shape control, surface modification, and controllable drug loading and release. Multi-faceted properties are imparted to the engineered nanoparticles, like magnetism, near-infrared absorption, photothermal efficiency, and suitable size and shape. This report presents nickel sulfide and dysprosium-doped nickel sulfide nanoparticles with poly-β-cyclodextrin polymer coating. The nanoparticles belong to the orthorhombic crystal systems, as indicated by X-ray diffraction studies. The size and shape of the nanoparticles are investigated using Transmission Electron Microscope (TEM) and a particle-size analyzer. The particles show soft ferromagnetic characteristics with definite and moderate saturation magnetization values. The nickel sulfide nanoparticles' in vitro anticancer and antibacterial activities are investigated in free and 5-fluorouracil/penicillin benzathine-loaded forms. The 5-fluorouracil-encapsulation efficiency of the nanoparticles is around 87%, whereas it is above 92% in the case of penicillin benzathine. Both drugs are released slowly in a controlled fashion. The dysprosium-doped nickel sulfide nanoparticles show better anticancer activity, and the efficacy is more significant than the free drug. The nanoparticles are irradiated with a low-power 808 nm laser. The dysprosium-doped nickel sulfide nanoparticles attain a higher temperature on irradiation, i.e., above 59 °C. The photothermal conversion efficiency of this material is determined, and the significance of dysprosium doping is discussed. Contrarily, the undoped nickel sulfide nanoparticles show more significant antibacterial activity. This study presents a novel designed nanoparticle system and the exciting variation of properties on dysprosium doping in nickel sulfide nanoparticles.
... The β-CD polymer (poly-CD) was synthesized via a reported procedure [23]. A hydrothermal synthesis method was employed to synthesize poly-CD-coated CuCo 2 S 4 NPs. ...
Nanocarriers of anticancer drugs are delicately designed with precision addition at every attempt. In this paper, we report CuCo2S4 nanoparticles that show light absorption in the near infrared-II wavelength range and possess magnetic characteristics. The synthesized nanoparticles are characterized by X-ray diffraction, Scanning Electron Microscopy, Dynamic Light Scattering, Thermogravimetry, and X-ray Photoelectron spectroscopy methods. The nanoparticles form a composite with biocompatible polymeric β-cyclodextrin. The nanoparticles possess a band gap energy of 2.25 eV. The magnetic property arises due to the cobalt incorporation in the nanoparticles. The anticancer drug camptothecin is loaded in the nanocarrier with an 89% adsorption efficiency. The in vitro release of the drug occurs in a sustained fashion. Further, the in vitro anticancer potential of the nanocarrier is examined on breast cancer (MDA-MB-231) cell lines, and the activities of the free- and the drug-loaded nanocarrier is compared. The cobalt-containing copper sulfide nanoparticle-poly-β-cyclodextrin composite works as a promising nanocarrier of camptothecin.
... The preparation was carried out according to the previously reported procedure [38]. Briefly, 2.25 g of NaOH was dissolved in 15 mL of deionized water (0.15% w/w) followed by adding 10 g of β-CD, and the mixture was stirred at 65 °C all night to activate the hydroxyl of β-CD. ...
Hydrogel dressings provide a moist wound healing environment, absorb the exudates of the wound, and have better biocompatibility than traditional dressings. However, it is still difficult to meet the needs of modern medicine due to the defects in drug burst release, weak mechanical strength, and poor water retention. To solve these problems, we developed a double-layer (DL) hydrogel based on β-cyclodextrin polymer (β-CDP), poly(vinyl alcohol) (PVA), and carboxymethyl cellulose sodium (CMC) via a layer-by-layer method. Inspired by natural coconut, this hydrogel consisted of a drug release layer (DRL) and a mechanical support layer (MSL). In our design, the introduction of β-CDP into the DRL slowed the drug release rate of the DL hydrogel. Furthermore, the mechanical strength of the hydrogel was improved by immersing the MSL in a calcium chloride/boric acid solution. Combining these two layers, the tensile strength and elongation at break of the DL hydrogel reached 1504 kPa and 400%, respectively. More interestingly, the release mechanism of DL hydrogel conformed to the diffusion–relaxation–erosion model, which was different from traditional hydrogel dressings. Therefore, the as-prepared DL structure represents a feasible solution for fabricating high-performance mechanical hydrogel dressings with sustained drug release properties, and the DL hydrogel has potential to be used for medical dressings applied in daily life.
... After cooling, the mixture was sonicated for an hour after the addition of 0.5 g NaOH in 15 ml water and dried. Poly-CD was prepared via a reported procedure [12]. The nanomaterial and polymer (1:2) were sonicated and the product was dried. ...
Metal nanoparticles possess a single element, thus minimizing the complexity and toxicity. It is fascinating to develop newer metal nanomaterials for such applications. We report, for the first time, a systematic synthesis and characterization of neodymium nanorods. Their broad spectral response extends from the UV-vis to the NIR-II wavelength range. The nanorods are paramagnetic. They are made as a nanocarrier by coating them with a poly-β-cyclodextrin polymer. The release of the loaded camptothecin on the nanocarrier takes place over a period of 300 hours. The anticancer efficiency of the camptothecin-loaded on the nanocarrier is reported. Since the neodymium nanoparticles possess a high aspect ratio, absorb light in the NIR wavelength range, and possesses a photoluminescent property. they can emerge as a new nanomaterial of interest in the fields of anticancer drug delivery and photothermal therapy.
... β-CDP was synthesized according to the literature. 29 The results of Fourier transform infrared spectroscopy (Figure S1), the particle size distribution ( Figure S2), and the ζ potential diagram ( Figure S3) proved that β-CDP had been successfully synthesized. The detailed experimental procedures and characterization are described in the Supporting Information. ...
The extensive use of organophosphorus pesticides in agriculture poses a high risk to human health and has boosted the demands for developing sensitive monitoring methods. Herein, we developed a facile and sensitive method for isocarbophos detection based on the remarkable fluorescence enhancement of pyrene during host-guest interaction of β-cyclodextrin polymer (β-CDP) and pyrene. The 3'-pyrene-labeled isocarbophos aptamer could be cleaved by exonuclease I to obtain free pyrene that was tagged on mononucleotides, which could enter the hydrophobic cavity of β-CDP, resulting in a prominent fluorescence enhancement. While the target isocarbophos was added, aptamer could undergo a conformational change into a hairpin complex, which prevented the cleavage and host-guest interaction because of the steric hindrance, leading to a weak fluorescence. The isocarbophos has been sensitively and selectively analyzed by detecting the system fluorescence intensity with a detection limit as low as 1.2 μg/L. In addition, we have verified the ability of our proposed method in real sample detection from fruit extract.
... The β-CD polymer (poly-CD) was synthesized via a reported procedure. 23 A hydrothermal synthesis method was employed to synthesize poly-CD-coated CuCo 2 S 4 NPs. Copper chloride and thiourea was mixed in the ratio 1:3 respectively in 20 ml deionized water and subjected to stirring for 15 minutes. ...
Nanocarriers of anticancer drugs are delicately designed with precision addition at every attempt. In this paper, we report CuCo 2 S 4 nanoparticles that show light-absorption in the NIR-II wavelength range and possess magnetic characteristics. The synthesized nanoparticles are characterized employing XRD, SEM, DLS, TGA, and XPS methods. The nanoparticles form a composite with biocompatible polymeric β-cyclodextrin. The nanoparticles possess a band gap energy of 2.25 eV. The magnetic property arises due to the cobalt-incorporation in the nanoparticles. The anticancer drug, camptothecin, is loaded in the nanocarrier with an 89% adsorption efficiency. The in vitro release of the drug occurs in a sustained fashion. Further, the in vitro anticancer potential of the nanocarrier is examined on breast cancer (MDA=MB-231) cell lines and the activities of the free- and the drug-loaded nanocarrier are compared. The cobalt-containing copper sulfide nanoparticle-poly-β-cyclodextrin composite works as a promising nanocarrier of camptothecin.
Nanocarriers that respond to the magnetic field are explored for their potential to deliver anticancer drugs and enhance chemotherapeutic efficacy. In this paper, we report NIR-II radiation-absorbing and magnetically-responsive rod-shaped CuFe2S3 nanoparticles (NPs) as drug delivery agents. The NPs are characterized by employing imaging and spectroscopic techniques. The CuFe2S3 NPs are coated with a synthesized poly-β-cyclodextrin polymer. The size and shape of the NPS are determined. The transmission electron microscopic imaging reveals the rod shapes of the NPs. The magnetic properties are studied and superparamagnetic behavior is observed. The chemotherapeutic drug, i.e, camptothecin (CPT) is loaded on the nanocarrier. The polymer-coated NPs are observed to possess an excellent CPT adsorption of about 98%. The in-vitro CPT-release kinetics is investigated for about 320 hours. The nanocarrier is loaded with CPT and tested for anticancer potential against breast cancer (MDA-MB-231) cell lines. In addition, the cell inhibition mechanism is studied and the apoptotic extent is elaborated. The performance of the poly-CD-coated CuFe2S3 NPs as a CPT-carrier is explored in detail and discussed.
Currently, reducing the formation of calcium scale is an important challenge for seawater utilization in the cooling water system of offshore oil and gas platforms. The combination of linear carboxymethyl β-cyclodextrin-epichlorohydrin polymer (L-CM-β-CD-EP) and citric acid-dopamine-epichlorohydrin polymer (CA-DA-EP) as an eco-friendly scale inhibitor was studied by the static experiments. We observed that L-CM-β-CD-EP/CA-DA-EP displayed excellent scale inhibition efficiency of 94.6% and 92.5% against CaCO3 and CaSO4, respectively, at the 19.2 mg/L inhibitor (Ca²⁺ =CO32-= 2400 mg/L, Ca²⁺ = SO42-= 800 mg/L). XRD and SEM images of scale crystal exhibited that CaCO3 and CaSO4 crystals were deformed and transformed by L-CM-β-CD-EP/CA-DA-EP, which was attributed to multiple inhibition effects, including lattice distortion, chelation, and host-guest synergistic effects. More importantly, the host-guest synergistic effects of L-CM-β-CD-EP and CA-DA-EP can significantly improve the scale inhibition performance of L-CM-β-CD-EP/CA-DA-EP. Besides, the TOC results analysis showed that L-CM-β-CD-EP/CA-DA-EP possessed excellent biodegradability, low bioaccumulation, and ecotoxicity.
L’infarctus du myocarde est l’une des maladies les plus meurtrières dans le monde aujourd’hui. En cas de survie, le cœur du patient reste fragilisé dû à un amincissement de la paroi myocardique. Dans ce contexte, l’objectif de cette thèse a été de concevoir un patch biofonctionnalisé par des facteurs trophiques connus pour leurs propriétés bénéfiques sur la régénération du myocarde. Lors de son utilisation, le patch sera alors positionné sur la paroi amincie et devra permettre d’apporter un soutien mécanique au tissu lésé. Dans un premier temps, des patchs non enrichis, élaborés à partir d’hydrogel physique de chitosane, ont été étudiés de façon à définir quel type d’hydrogel était le plus approprié. Pour cela, après une étude des propriétés mécaniques des hydrogels de chitosane de différents degrés d’acétylation, les propriétés biologiques de ces biomatériaux ont pu être évaluées chez le rat sur un modèle d’infarctus du myocarde en phase chronique. L’adsorption des biomolécules dans les gels a également été étudiée, d’abord avec une protéine modèle (BSA), puis avec un cocktail de facteurs trophiques contenus dans les sécrétions de cellules souches mésenchymateuses (sécrétome). Le choix des sécrétomes s’est fait à partir d’une étude in vitro, dans laquelle certaines sécrétions ont montré une capacité à protéger les cardiomyocytes primaires en culture. Le patch hydrogel précédemment sélectionné a pu être enrichi par deux types de sécrétomes et implanté in vivo chez le rat. Les études chez l’animal nous ont permis de définir l’association patch hydrogel / sécrétome la plus prometteuse permettant une amélioration de la fonction cardiaque après 30 jours de traitement
Aim: This study aims at tuning the properties of the nanoparticles by incorporating neodymium, exploring the sustained release of drug, and the anticancer activity on breast cancer cells.Methods: The crystal characteristics of NdCuS2 nanoparticles are analyzed using X-ray diffraction. The morphology and size of the nanoparticles were characterized using Transmission Electron Microscope and particle size analyzer. The rate of release of the encapsulated camptothecin and anticancer effects on breast cancer cells are investigated.Results: The nanoparticles are rod-shaped, 132 ± 8 nm long and 27 ± 7 nm wide. The band gap of the nanoparticles is 4.85 eV. The drug encapsulation efficiency is 94.76% (w/w). The drug is released in a sustained manner, over a period of 180 hours. The cytotoxicity of the camptothecin-loaded NPs is examined on MDA-MB-231 cells and the IC50 is 4.39 µg mL-1Conclusion: The NdCuS2 nanoparticles are promising as theranostic agents considering their material characteristics and anticancer activity.
The use of cisplatin is restricted by systemic toxicity and drug resistance. Supramolecular nano-drug delivery systems involving drugs as building blocks circumvent these limitations promisingly. Herein, we describe a novel supramolecular system [Pt(IV)-SSNPs] based on poly(β-cyclodextrin), which was synthesized for efficient loading of adamantly-functionalized platinum(IV) prodrug [Pt(IV)-ADA2] via the host-guest interaction between β-cyclodextrin and adamantyl. Pt(IV)-ADA2 can be converted to active cisplatin in reducing environment in cancer cells, which further reduces systemic toxicity. The introduction of the adamantane group-tethered mPEG2k endowed the Pt(IV)-SSNPs with a longer blood circulation time. In vitro assays exhibited that the Pt(IV)-SSNPs could be uptaken by CT26 cells, resulting in cell cycle arrest in the G2/M and S phases, together with apoptosis. Furthermore, the Pt(IV)-SSNPs showed effective tumor accumulation, better antitumor effect, and negligible cytotoxicity to major organs. These results indicate that supramolecular nanoparticles are a promising platform for efficient cisplatin delivery and cancer treatment.
Herein, we report a neodymium-doped carbon dot composite with a poly-β-cyclodextrin. It possesses wavelength-dependent photoluminescence characteristics. In addition, the material displays magnetic characteristics due to the doped neodymium element. The nanocomposite is soluble in water and accommodates the anticancer drug, camptothecin. The release of the loaded drug is pH-dependent. Further, the anticancer activity of the free- and the drug-loaded carrier are studied on MCF-7 cells. The biological activity and the luminescence and magnetic properties of the nanocarrier are demonstrated.
Photodynamic therapy (PDT) is a promising and non-invasive treatment for various cancers. Although nuclear PDT has considerable therapeutic prospects, it is still hindered by the non-specific recognition of tumor tissues or the degradation of nuclear targeting cationic groups by enzymes in the blood. Herein, a hierarchical targeted and controlled release strategy is proposed by using folate-modified poly-β-cyclodextrin (poly-β-CD) as a nano-carrier for loading nuclear localization signals (NLSs)-conjugated photosensitizer PAP (PAP = pyropheophorbide a—PAAKRVKLD). Excitingly, the obtained FA-CD@PAP (FA = folic acid) and nanoparticles (NPs) can specifically recognize tumor cells overexpressing folate receptors (FR) to remarkedly enhance the intracellular accumulation. Furthermore, the encapsulated PAP can be released under acidic conditions to realize precise nuclear localization. The reactive oxygen species (ROS) generated by the intranuclear-accumulated PAP upon irradiation can oxidize and destroy DNA chains or DNA repair enzymes instantaneously, which can directly induce cell death. As a result, FA-CD@PAP NPs exhibit excellent tumor regression and negligible side effects. This work provides an intelligent nuclear-targeted delivery strategy for in situ nuclear PDT with extremely prominent efficacy and high biological safety.
The regeneration of diabetic bone defects remains challenging as the innate healing process is impaired by glucose fluctuation (GF), reactive oxygen species (ROS) and over-expression of proteinases (such as matrix metalloproteinases, MMPs). A “diagnostic” and therapeutic dual logic-based hydrogel for diabetic bone regeneration is therefore developed through the design of a double-network hydrogel consisting of phenyboronic acid-crosslinked polyvinyl alcohol and gelatin colloids. It exhibited a “diagnostic“ logic to interpret pathological cues (GF, ROS, MMPs) and determine when to release drug in a diabetic microenvironment and a therapeutic logic to program different cargo release to match immune-osteo cascade for better tissue regeneration. The hydrogel was also shown to be mechanically adaptable to the local complexity at the bone defect. Furthermore, the underlying therapeutic mechanism was elucidated whereby the logic-based cargo release enabled the regulation of macrophage polarization by remodeling the mitochondria-related antioxidative system, resulting in enhanced osteogenesis in diabetic bone defects. In conclusion, our study provides critical insight into the design and biological mechanism of dual logic-based tissue engineering strategies for diabetic bone regeneration.
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Injectable hydrogels have been studied as drug delivery systems because of their minimal invasiveness and sustained drug release properties. Pluronic F127, consisting of poly(ethylene oxide)-poly(propylene oxide)-poly(ethylene oxide) triblock copolymers, exhibits thermo-responsive properties and hence is injectable due to its rapid sol-gel transition. Unmodified Pluronic F127-based hydrogels, however, have limited long-term stability and controllable release of drugs entrapped within them. In this study, host-guest interactions between adamantane-conjugated Pluronic F127 (F127-Ad) and polymerized β-cyclodextrin (CDP) were employed to develop a hydrogel-based protein delivery system. Single or multiple adamantane units were successfully introduced at the termini of Pluronic F127 with a 100% conversion yield, and the synthesized F127-Ad polymer produced a physically crosslinked micelle-packing structure when mixed with CDP. As the number of adamantanes at the terminal ends of Pluronic F127 increased, the critical gelation concentration of F127-Ad/CDP hydrogel decreased from 15 to 6% (w/v). The F127/CDP hydrogel was able to maintain its structure even with lower polymer content, and its injectability improved with a reduction of the hydrogel viscosity. The long-term stability of F127/CDP hydrogels was evaluated in vitro and in vivo, and it was demonstrated that the subcutaneously injected hydrogel did not disintegrate for up to 30 d. Throughout the drug release test using gelatin and insulin as model drugs, it was demonstrated that their release rates could be regulated via complexation between the protein drugs and the β-cyclodextrin molecules inside the hydrogel. In conclusion, the F127-Ad/CDP hydrogel is expected to be a versatile protein delivery system with controllable durability and drug release characteristics.
Statement of significance
Pluronic F127 is one of the widely studied polymeric materials for thermo-sensitive injectable hydrogels due to its high biocompatibility and rapid sol-gel transition. Since the Pluronic F127-based hydrogel has some limitations in its long-term stability and mechanical property, it is inevitable to modify its structure for the application to drug delivery. In this study, mono- or multi- adamantane-conjugated Pluronic F127s were synthesized and mixed with β-cyclodextrin polymers to form hydrogels with host-guest interaction-mediated micelle-packing structures. The host-guest interaction introduced into the hydrogel system endowed it a sustained protein drug release behavior as well as high durability in vitro and in vivo. By increasing the number of adamantane molecules at the end of the Pluronic F127, both the stability and injectability of the hydrogel could be also modulated.
Vitreoretinal surgery is an essential approach to treat proliferative diabetic vitreopathy, retinal detachment, retinal tear, ocular trauma, and macular holes. The removal of the natural vitreous and the replacement with substitutes are critical steps for retina reattachment. Vitreous substitutes including silicone oil (SiO), air, sulfur hexafluoride (SF6), and perfluoropropane (C3F8), have been widely applied in clinical practice. However, these substitutes are reported to cause complications such as emulsification, high intraocular pressure, and lens opacification. Polymeric hydrogels are a kind of material with favorable physical, mechanical properties, and adaptable biocompatibility, thus being highly expected to be ideal vitreous substitutes. Despite years of research, very few polymeric hydrogels can be applied practically in the vitreous cavity. In this review, we focus on the development of polymeric natural-based hydrogels and synthetic hydrogels. Particularly, we sought to focus on recent advances in the novel stimuli-response and self-assembly supramolecular hydrogels. Characterized by easy injectability and long residence time, this kind of hydrogel became the potentially promising candidates for ideal vitreous substitutes. Finally, we evaluate the current challenges and provide the future directions of vitreous substitutes.
Hydrogels are a kind of soft and wet materials, which have three-dimensional network structures formed by polymers or small molecules in water through self-assembly or chemical cross-linking. Hydrogels can be divided into two categories of chemical and physical hydrogels according to the ways of hydrogel formation. The chemical hydrogels containing covalent bonds have high chemical resistance and thermodynamic stability. However, they are usually nondegradable and unrecyclable due to the irreversibility of covalent bonds, which limits their practical application. By contrast, various stimuli-responsive hydrogels based on supramolecular interactions or dynamic covalent bonds have become the research focus in recent years. These studies expand the application of hydrogels in drug delivery, biosensing, shape memory, etc. However, the classical responsiveness of the hydrogels is relatively passive, which always requires an external stimulus to induce the assembly or disassembly of the hydrogel networks and lacks the ability of self-regulation. Self-regulating systems are very common in living organisms, such as the reversible formation of intracellular actin. The non-equilibrium dynamic processes generate transient assemblies, which inspires the researchers to design artificial non-equilibrium systems. In 2010, a transient supramolecular hydrogel mediated by chemical fuels was presented for the first time. In the following decade, the researchers have been exploring how to mimic the living systems by simply mixing chemical reagents to build artificial non-equilibrium systems. The emergence of transient hydrogels is a significant breakthrough in the field of smart hydrogel materials. In the system, a switch that can induce sol-gel transitions autonomously is set up, which endows the soft materials with autonomy or adaptability. The scientists have realized the versatile regulation of the structure, function and lifespan of the hydrogels by imitating the complex living systems and combining the existing biocatalytic and/or chemical reactions. For example, for injectable biomaterials, the precise control on the lifetime of the transient hydrogels contributes to the timed release of drugs. Moreover, the transient hydrogels can also be used as temporary seals or adhesives for biomedical applications. At the same time, the remote-controlled time programmability is of great significance for the in situ study of self-assembly in closed systems. Although the research on transient hydrogels is still in its infancy, the advanced characteristics of the transient hydrogels, as well as the spatiotemporal regulation mode for the precise control of material properties, suggest that the transient hydrogels will be an important class of intelligent soft materials useful in many fields such as drug delivery, data encryption, material repairing and reprocessing in the future. In short, the transient hydrogel systems regulated by the chemical reaction networks are one of the important results inspired from the dissipative assembly in living systems. They significantly broaden the application range of hydrogels. In general, the current research in the field of transient hydrogels mainly focuses on the expansion of transient hydrogel systems and the design of transition modes, which requires a deeper understanding of the hydrogel formation mechanisms. Therefore, it is necessary to make a systematic summary for this rapidly developing field at this point. In this review, we give a clear definition of transient hydrogels: transient hydrogels refer to water-based temporary gels formed in non-equilibrium states, which can spontaneously convert to sol states mediated by internal reactions. According to the difference in hydrogel formation mechanisms, the classification of hydrogels is presented. Furthermore, the existing transient hydrogel systems are reviewed in detail. The application and limitation of transient hydrogels are summarized, and the future development direction is discussed and prospected lastly in this review.
High strength and ductility materials are demand for modern various applications. In order to surmount the inherent trade-off between toughness and stiffness for most elastomers, we developed a strategy which...
We report on the fabrication of a high performance multi-functional supercapacitor which is intrinsically stretchable, self-healable, and photodegradable. A repeatedly stretchable (500 times), photodegradable hydrogel that self-heals quickly at room temperature without any trigger is synthesized by crosslinking of azobenzeno-polyacrylamide (Azo-PAM) and water-soluble α-cyclodextrin polymer (α-CDP) via dynamic host-guest interaction. With the Azo-PAM/α-CDP/LiCl hydrogel as polyelectrolyte, the stretchable, self-healable, and photodegradable supercapacitor is fabricated. After complete bisection, the supercapacitor recovers its electrochemical performance by physical contact in air-ambient conditions and maintains its performance upon multiple cycles of self-healing at a single bisected location. It also maintains elastic performance even after repeated stretching and self-healing. Finally, the supercapacitor exhibits photodegrading performance, dissolving in water upon UV-irradiation after use. This work demonstrates the superior performance and high potential of our newly devised stretchable, self-healable, and photodegradable supercapacitor as a smart energy storage device for next-generation durable and eco-friendly wearable electronics.
It has been attracted broad interest to construct stimulus responsive supramolecular hydrogels as smart materials over the past few decades; however, the design of multi-stimuli responsive hydrogels remains a formidable challenge. Herein, a multi-stimuli responsive supramolecular hydrogel has been designed on the basis of methoxy-azobenzene-grafted poly(acrylic acid) (PAA-mAzo) and β-CD dimer, which involves the host-guest and electrostatic interactions. Besides the common thermo-responsive behavior, the hydrogel also exhibits reversible sol-gel transition under green and blue light irradiations because of the disassociation and association of host–guest interaction between mAzo and β-CD. In addition, the hydrogel turns into precipitate at low pH due to the decrease of solubility of PAA in aqueous solution. The electrostatic interaction between the negatively charged carboxylic acid groups and hydrated protons at high pH makes the recovery of hydrogel. At last, the release of rhodamine B loaded in the triple-stimuli responsive hydrogel can be accelerated by green light irradiation and low pH, which demonstrates the potential applications in biomedical materials.
Calcium ion (Ca²⁺) has proven to be the second messenger that is directly related to diverse normal biochemical functions and pathological processes. Thus, understanding the critical functions and dynamics of endogenous Ca²⁺ at cellular and animal levels is highly demanded. However, reliable fluorescence detecting and imaging strategies are usually challenging to achieve with high sensitivity, low background signal, and high imaging resolution for Ca²⁺ detecting and imaging analysis in vivo. Inspired by supramolecular self-assembly strategy, we herein report a novel supramolecular near-infrared (NIR) fluorescent nanosensor (NIRCD-Ca) for Ca²⁺ detecting and imaging analysis in vitro and in vivo with three parts: a guest NIR-fluorophore was labeled an adamantane moiety, a host supramolecular equipped with β-CD polymers, and a calcium ion chelating site of O,O'-Bis(2-aminophenyl)ethyleneglycol-N,N,N',N'-tetraacetic acid (BAPTA) as a fluorescence quenching moiety by photoinduce electron transfer effect (PET-effect). In the present work, NIRCD-Ca exhibits excellent water solubility and biocompatibility, very low background fluorescence with a significant ∼18-fold fluorescence intensity enhancement in the presence of Ca²⁺, superb resolution for mice imaging by NIR-emission, as well as extreme low detection line as low as 9.7 nM. All these features are favorable for detecting of Ca²⁺ in complex biological samples and applying for NIR imaging of Ca²⁺ in mouse model directly with satisfactory sensitivity, suggesting that the NIRCD-Ca is an ideal effective nanosensor for Ca²⁺ detecting and imaging analysis in biosystems. Furthermore, the nanosensor NIRCD-Ca has potentiality to become an essential detection technique for the investigation of signaling pathways involving Ca²⁺ in biosystems.
Vitreous endo-tamponades are commonly used in the treatment of retinal detachments and tears. They function by providing a tamponading force to support the retina after retina surgery. Current clinical vitreous endo-tamponades include expansile gases (such as sulfur hexafluoride (SF6) and perfluoropropane (C3F8)) and also sislicone oil (SiO). They are effective in promoting recovery but are disadvantaged by their lower refractive indices and lower densities as compared to the native vitreous, resulting in immediate blurred vision after surgery and necessitating patients to assume prolonged face-down positioning respectively. While the gas implants diffuse out over time, the SiO implants are non-biodegradable and require surgical removal. Therefore, there is much demand to develop an ideal vitreous endo-tamponade that can combine therapeutic effectiveness with patient comfort. Polymeric hydrogels have since attracted much attention due to their favourable properties such as high water content, high clarity, suitable refractive indices, suitable density, tuneable rheological properties, injectability, and biocompatibility. Many design strategies have been employed to design polymeric hydrogel-based vitreous endo-tamponades and they can be classified into four main strategies. This review seeks to analyse these various strategies and evaluate their effectiveness and also propose the key criteria to design successful polymeric hydrogel vitreous endo-tamponades.
In this study, the nanocables were prepared by the supramolecular self-assembly interaction between polyaniline (PANI) and linear carboxymethyl-β-cyclodextrin polymer functionalized carbon nanotubes (L-CM-β-CD-P-CNTs). Its morphological, thermal, structural, and electrochemical properties were analyzed by using different instrumental techniques. As expected, the PANI/L-CM-β-CD-P-CNTs supramolecular nanocables exhibited excellent electrochemical performance and cycling stability. More importantly, the specific capacitance (SC) values for PANI/L-CM-β-CD-P-CNTs reached 996 F g⁻¹ at a current density of 1 A g⁻¹. In addition, the PANI/L-CM-β-CD-P-CNTs supramolecular nanocables exhibited 90 % capacitance retention after 15,000 charge-discharge cycles.
We report a novel double cross-linked hydrogel system based on polyacrylamide and poly(2-methyl-2-oxazoline) (PMOXA) network chains, as well as on supramolecular host–guest interactions with on-demand tailored mechanical properties. Well-defined vinyl-bearing PMOXA macromonomers, functionalized with either β-cyclodextrin units (β-CD–PMOXA) or adamantane units (Ada–PMOXA), were synthesized and confirmed using ¹H NMR, MALDI-TOF-MS and GPC measurements. The complexation between adamantane and β-CD modified macromonomers in solution towards bismacromonomers was confirmed by 2D NOESY NMR and DLS. After introducing these bismacromonomers into the polyacrylamide hydrogel, the supramolecular non-covalent Ada/β-CD bond was responsible for the presence of PMOXA network chains to form a dense network. Once the interactions broke, the PMOXA chains no longer contributed to the network, but became dangling graft side chains in a predominated polyacrylamide network. Their dissociative nature influenced the physical properties, including the swelling behavior and mechanics of the final hydrogel. Rheological experiments proved that the E-modulus of the network was significantly increased by the supramolecular host–guest interactions. Tuning the lengths of PMOXA network chains even allowed the modification of the changes in mechanical strength, also through the addition of free β-CD. The tunable properties of the double cross-linked supramolecular hydrogel proved their unique strength for future applications.
The development of tough, self-healing materials is a notable accomplishment. Previously, self-healable materials were soft materials with a tensile stress less than 10 MPa. Herein, we describe citric-acid-modified cellulose (CAC)-based composites that are tough, stretchable, and self-healing. These properties are due to two kinds of non-covalent bonds from host-guest interactions between cyclodextrin (CD) derivatives that act as host units and alkyl derivatives with carboxyl ended groups that act as guest units which hydrogen bonding (H-bonding) with the carboxyl or hydroxyl groups in CAC. The host-guest interactions and H-bonding from the CAC-based composites material show a high energy dissipation that results in a high tensile stress (21 MPa) and high fracture energy (151 MJ·m-3) which are comparable to those in commercially available low-density poly(ethylene) (LDPE). The reinforcement increases the mechanical properties by ten times compared to those of the polymer without CAC. In addition to the high fracture energy, the CAC-based composites also show high stretchability and reach a strain of 1000%, which is usually reported in the 10% scale for composite materials. These two kind of bonds also show interesting self-healing properties for the CAC-based composites. The self-healing ratio for the CAC-based composites is 56% at room temperature and 84% at 80°C. This study successfully demonstrates that CAC-based composites using host-guest interactions and H-bonding show toughness, stretchability, and a self-healing capability.
Cyclodextrins (CDs) are cyclic oligosaccharides with unique conical structure enabling host-guest inclusion complexes. However, virgin CDs are suffering from low solubilities, lack of functional groups and not strong complexation with guests. One of the most efficient ways to improve the properties of cyclodextrins is the synthesis of polycyclodextrins. Generally, there are two types of polycyclodextrins: 1) polymers containing CD units as parts of the main backbone; and 2) polymers with CD units as side chains. These polycyclodextrins are produced from direct copolymerization of virgin cyclodextrins or cyclodextrins derivatives with various monomers including isocyanates, epoxides, carboxylic acids, anhydrides, acrylates, acrylamides and fluorinated aromatic compounds. By selecting the proper derivatives of CDs and controlling the polymerization, polycyclodextrins with linear, hyperbranched, and crosslinked structures have been synthesized. Polycyclodextrins have found significant applications in numerous areas, as adsorbents for removal of organic pollutants, carriers in gene/drug delivery, and for preparation of supramolecular based hydrogels.
Hydrophilic polymeric materials with movable cross-linkers were obtained by the bulk copolymerization of a hydrophilic cyclodextrin monomer (γCDAAmMe) and liquid acrylamide monomers. A 2D ¹H-NOESY NMR study revealed that the main chains penetrated the CD ring units, which acted as movable cross-linking points. Copolymerization of γCDAAmMe with N,N-dimethyl acrylamide (DMAA) as a small main chain monomer results in hydrophilic movable cross-linked materials (pDMAA-γCDAAmMe (x)). On the other hand, using 4-acryloylmorpholine (ACMO) or N,N-dimethylaminopropyl acrylamide (DMAPAA) as a bulky main chain monomer disfavours the formation of movable cross-links due to steric hindrance between γCDAAmMe and the side chains. In the water content range of approximately 40–80 wt%, the Young's moduli of pDMAA-γCDAAmMe (1)s are similar to those of pDMAA-MBAAm (1). However, the fracture energy of movable cross-linked materials is higher than that of than materials covalently cross-linked with N,N′–methylenebis(acrylamide) (MBAAm). An addition of water enhanced the mobility of the main chain polymers, allowing the movable cross-linking points.
Accurate and sensitive imaging of hypoxia associated with inflammatory bowel disease (IBD) is significant for precise diagnosis and treatment of this disease, but it remains a challenge for traditional hypoxia-activatable fluorescence probes because of more moderate hypoxic state during IBD than under other pathological conditions. To address this issue, herein, we design a hypoxia-activatable and cytoplasmic protein-powered fluorescence cascade amplifier, named HCFA to image of hypoxia associated with IBD in vivo. In our design, 4-aminobenzoic acid (azo)-modified mesoporous silica nanoparticle (MSN) was used as container to load black hole quencher 2 (BHQ2) and cytoplasmic protein-binding squarylium dye (SQ), then the -cyclodextrin polymer (-CDP) combined with azo through host-guest interaction to form HCFA. Upon passive stagnate in inflamed tissue of IBD, the azo band would be cleaved under hypoxic microenvironment and SQ was released to activate the fluorescence of HCFA. Moreover, the unconstrained SQ can bind with cytoplasmic protein to exhibit drastic fluorescence intensity enhancement, realizing the fluorescence signal amplification for imaging of hypoxia. Take the advantage of large load capacity of MSN and unique property of SQ, HCFA can sense oxygen levels in the range of 0% to 10%. Meanwhile, the fluorescence imaging results demonstrate that HCFA can sensitively distinguish different levels of cellular hypoxia and monitor the variations of hypoxia in vivo, highlighting HCFA as a promising tool for detection of hypoxia associated with IBD.
Double network (DN) hydrogels with high strength and toughness have been developed as promising materials. In this paper, we prepared a novel κ-carrageenan/polyacrylic acid (κ-CG/PAA) DN hydrogel with excellent mechanical performances, which was achieved by dual cross-linking of the stiff first network. The obtained DN-1.956-0.1-2-15 hydrogels exhibited exceptional mechanical properties with fracture tensile stress of 2.53 MPa, fracture strain of 1381.91% and toughness of 13.40 MJ/m³. The results showed that dual cross-linking of κ-CG (double-helical junctions and metal coordination bonds) was conductive to high strength and toughness. Moreover, due to their totally physically cross-linking structures, the hydrogels showed 67% recovery of toughness after 2 min. Furthermore, the DN hydrogels showed self-healing capability, shape-memory ability, as well as excellent cytocompatibility and biodegradability. Such a designed DN hydrogel realizes the essential integration of improved mechanical properties, good biocompatibility and biodegradation for developing a desired scaffold material for potential tissue engineering applications.
Osmotic power generation has emerged as an advanced technology toward water-energy nexus to tackle global water pollution. It provides a sustainable use of salinity gradient from water resources yet encounters major obstacles caused by pressure-retarded osmosis (PRO) membrane fouling. Although membranes with good antifouling properties are widely studied, their antifouling functions are readily lost when scratches or detachments occur through physical damage during operation and chemical degradation by water and corrosive foulants. Consequently, it is important to develop antifouling membranes with autonomous self-healing capabilities. Herein, self-healable functionalized poly(ether sulfone) (PES) antifouling membranes have been fabricated via the sequential conjugation of the zwitterionic random copolymer [poly(1-(1-(1-adamantylcarbonyloxy)methyl)-3-vinylimidazolium bromide-co-1-(3-sulfopropyl)-3-vinylimidazolium-co-vinylamine)] (P(ADVI-co-SBVI-co-VA), abbreviated as PASV copolymer) and linear cyclodextrin polymer (LPCD) on polydopamine-preactivated PES supports. The self-healing behaviors rely on the judiciously designed "button-and-buttonhole" supramolecular network. Specifically, β-cyclodextrins in LPCD and adamantines in PASV act as "buttonholes" and "buttons", respectively. Under physical and chemical damages, the β-cyclodextrin "buttonhole" may sacrificially detach from the adamantine "button" of PASV but then recap another adamantine to restore the protective function. The antifouling and self-healing traits of as-functionalized PES-g-PASV-LPCD membranes were demonstrated by the superior antiprotein behaviors and improved antimicrobial performances on both nonaged and aged samples. In the PRO process, the modified membranes were effective in mitigating organic fouling and exhibited higher power density (79% of the initial value) than the nonmodified ones (47% of the initial value) in municipal wastewater testing. The strategy for engineering inherently healable and antifouling membranes paves a new pathway for the development of sustainable membranes for osmotic power production.
In this work, surface-functionalized microcapsules from porous carbon nanospheres (PCNs) were successfully prepared by mussel-inspired chemistry with polydopamine (PDA) and metal-free photoinduced electron transfer–atom transfer radical polymerization (PET-ATRP). These functional microcapsules are introduced into self-healing hydrogels to enhance its mechanical strength. The PCNs synthesized by a simple soft template method are mixed with linseed oil (LO) for loading of the biomass healing agent and the microcapsules are first prepared by coating PDA. PDA coatings were used to immobilize ATRP initiator for initiating 4-vinylpyridine (4VP) on the surface of microcapsules by PET-ATRP. Using these functional microcapsules, the self-healing efficiency was about 92.5% after 4 hrs at ambient temperature and the healed tensile strength can be held at 2.5 MPa with a fracture strain of 625.2%. All results indicated that the surface-functionalized microcapsules for self-healing hydrogels have remarkable biocompatibility and mechanical properties.
Addition of a water soluble β-cyclodextrin polymer to an aqueous solution of an amphiphilic polymer has given the birth to a new class of associating polymer systems. The β-cyclodextrin polymers are used to promote the associations between amphipathic polymer chains by formation of inclusion complexes between the hydrophobic moieties and the β-cyclodextrin cavities. In this study, the water-soluble β-cyclodextrin polymers were formed by polycondensation of the monomer with epichlorohydrin. The amphipathic polymers are hydrophilic chains which have been modified by introducing hydrophobic moieties. The latter can be either rigid (adamantyl groups) or flexible structures (alkyl chains with more than 12 carbon atoms) but they must possess a strong affinity for β-cyclodextrin cavities. The influence of the chemical nature and the architecture of the amphipathic copolymer has been studied in order to elucidate the mechanisms of associations between these polymers. Different architectures have been studied: comblike polymers (hydrophobically modified dextran) and star polymers (hydrophobically end-capped star polyethyleneoxide). Polyelectrolytes have also been synthesized (hydrophobically modified degradable copolyesters). In this case, the associations show high sensitivity to pH and ionic strength. The hydrophobic molar ratio of the amphipathic polymer, as well as the respective concentrations of each polymer play a central role in determining the associating properties of the system. The associations have been studied by viscosity, rheology and dynamic light scattering measurements. Polymer networks are obtained above critical values of the number of hydrophobic groups per chain and are physical gels possessing original rheological properties because the microscopic association is reversible. Another alternative provided by the attractive interactions which generate the inclusion complexes is the possibility of associative phase separation. Phase separation takes place, in the case of neutral systems, when the number of hydrophobic moieties per chain is larger than 3.
Host polymers with pendant β-cyclodextrin side groups and guest polymers with pendant hydrophobic 4-t-butyl anilide side groups were synthesized by polymer analogous reactions starting fromcopolymers of maleic anhydride. The host guest interaction of these polymers with suitable monomeric counterparts was proven bytitration microcalorimetry. The interaction of the host polymer and the guest polymer in aqueous solution leads to a tremendous increase in viscosity. Polymer chains appear to form a physical network due to host guest interactions. This interaction can be switched off either by dilution or by addition of a competitive monomeric host or guest.
Using molecular recognition of α-cyclodextrin (α-CD), we have successfully constructed a photoresponsive hydrogel system by combination of simple components, α-CD, dodecyl (C12)-modified poly(acrylic acid) (p(AA/C12)), and a photoresponsive competitive guest, 4,4‘-azodibenzoic acid (ADA). An aqueous solution of p(AA/C12) exhibited a gel-like behavior because polymer chains form a network structure via hydrophobic associations of C12 side chains. When α-CD was added to the gel-like aqueous solution, the gel was converted to a sol mixture because hydrophobic interactions of C12 side chains were dissociated by the formation of inclusion complexes of α-CD with C12 side chains. Upon addition of ADA to a binary sol mixture of p(AA/C12) and α-CD, α-CD interacted predominantly with ADA, and then hydrophobic associations of C12 side chains were restored, resulting in a sol-to-gel transition. When a ternary gel mixture of p(AA/C12), α-CD, and ADA was irradiated with UV light, ADA was isomerized from trans to cis, and the mixture underwent a gel-to-sol transition because α-CD formed inclusion complexes more favorably with C12 side chains than with cis-ADA. When the ternary sol mixture was irradiated with visible light, ADA was isomerized from cis to trans and the mixture underwent a sol-to-gel transition. Furthermore, these gel-to-sol and sol-to-gel transitions occurred repeatedly by repetitive irradiations of UV and visible light.
An original associating system is presented in this paper. It involves the mixing of two polymers: hydrophobically modified polyethylene oxide (PEO) and β-cyclodextrin copolymer. Inclusion complexes between the hydrophobic moieties (naphthalene or adamantane) and β-cyclodextrin cavities are at the origin of the attraction between the two polymers. The strength of the attractive interactions has been tailored by using different architectures for the amphiphilic polymer: linear or multi-arm branched PEO have been used, leading to a variable number of hydrophobic end-groups per chain. Interactions between the host and guest polymer have been demonstrated through both microscopic and macroscopic analysis of the properties of the medium: complexation constants have been determined by fluorescence methods and dialysis, while polymolecular associations have been evidenced by viscoelastic properties. Phase diagram studies have shown that the strength of the interactions between the two polymers is strongly related to the number of hydrophobic moieties per chain: while unmodified PEO and β-cyclodextrin copolymer are phase segregating, associative phase separations are observed for a number of hydrophobes per chain higher than or equal to three.
The effectiveness of cyclodextrins in polymer synthesis was investigated. The use of cyclodextrin to polymerize phenol derivatives using horse radish peroxidase as catalyst in the presence of H2O2 was also investigated. Results showed successful application of cyclodextrins in polymer synthesis in aqueous solution via free radical polymerization and oxidative recombination mechanism.
The homopolymerization of methylated-β-cyclodextrin (me-β-CD) host–guest compound of tert-butyl methacrylate (1a) is described. We investigated the free radical polymerization of the complexed monomer (1a) and of the free monomer (1) at ambient and high temperature. Poly(tert-butylmethacrylate) synthesized via the cyclodextrin mediated method exhibited number-average molecular weights ranging from 12,000–60,000 g/mol with polydispersities from 1.9–3.1. The polymerizations without cyclodextrin show significantly lower yields in comparison with the cyclodextrin mediated polymerizations. Here, the polymer obtained is colloidal dispersed. At ambient temperature (20°C) no polymerization occurs in the absence of cyclodextrin, whereas, under the same conditions, the homopolymerization of the complexed monomer (1a) leads to polymerization with yields around 75%.
The polymerization of hydrophobic monomers was carried out in aqueous medium by using cyclodextrins as the hydrophilic host component. By using chain-transfer agents, the degree of polymerization was effectively controlled.
A novel route to the formation of large aggregates, with associated rheological enhancement, is provided by formation of inclusion complexes between a telechelic polymer and a second polymer containing appropriate receptor groups. The main focus of this paper describes such complexes between an adamantane end-capped poly(ethylene oxide) (PEO) (Mw = 104 gmol-1) with a polymer of β-cyclodextrin (Mw = 3.5 × 104 gmol-1) as studied by light scattering. There is a pronounced broadening of the width of the particle size distribution with increasing concentration of end-capped polymer, accompanied by a strong increase in the average relaxation time. Viscosity enhancement in the system was measured on the same samples. Newtonian behavior was observed in the shear rate range 0.017−90 s-1. Light scattering experiments (static and dynamic) were also made on the telechelic PEO itself. Light scattering shows the presence of a slowly relaxing component which dominates the scattering and this reflects large structures (radius 80 nm) created by interchain association to form a loose network, albeit at low concentration. Static and time-resolved fluorescence experiments show that there is no detectable tendency for “micellization” of the adamantane groups.
A host polymer with pending beta-cyclodextrin side-groups and a guest polymer with pending hydrophobic 4-tert-butylanilide side groups were synthesized by polymer-analogous reactions starting from poly[(maleic anhydride)-alt-(isobutene)] ((M) over bar(w), = 60000). The inclusions of both polymers with complementary monomeric guests and hosts are proven by microcalorimetry. The interaction of the host polymer and the guest polymer in aqueous solution is accompanied by a tremendous increase in viscosity.
Eine nichtkovalente Vernetzung Adamantylgruppen tragender Copolymere von N-Isopropylacrylamid gelingt mit Cyclodextrin-Dimeren (siehe Bild). Hierdurch kommt es zur Bildung thermosensitiver Hydrogele, deren Trübungspunkte niedriger als die der unvernetzten Copolymere liegen. Bei Zugabe von monomerem methyliertem Cyclodextrin zu Lösungen der reinen Copolymere steigen die Trübungspunkte; dies hat jedoch kaum Einfluss auf die Viskosität der Polymerlösungen.
We report on the first examples of the free radical polymerization of a fluorinated 2‐vinylcyclopropane 1 and its copolymerization with an alkyl 2‐vinylcyclopropane 2 in aqueous solution via their host‐guest complexation with a random methylated β ‐cyclodextrin (RAMEB) using a water‐soluble initiator (VA50). Upon polymerization, the dethreaded cyclodextrin remained in water solution, whereas the water‐insoluble polymer precipitated out and was isolated. The polymers prepared exhibited mesophase behavior over a wide range of temperature. Both T g and T i of the copolymers increased linearly with the amount of fluorinated co‐units.
Complexation of fluorinated vinylcyclopropane 1 with RAMEB and polymerization in water solution.
magnified image Complexation of fluorinated vinylcyclopropane 1 with RAMEB and polymerization in water solution.
The chemical and enzymatic hydrolyses of 1,1-diethoxycarbonyl-2-vinylcyclopropane (1) were investigated. The product of the pig liver esterase (PLE)-catalyzed hydrolysis of 1 is a chiral trans monoester of 2-vinylcyclopropane dicarboxylic acid. New 1,1-disubstituted 2-vinylcyclopropane monomers (2a, b) were synthesized by the esterification of this ester. Methylated β-cyclodextrin was used to complex monomers 2a, b, yielding water-soluble 1 : 1 host/guest complexes. These complexes were polymerized in aqueous media by a free-radical ring-opening mechanism.
The polymerization of methylated β-cyclodextrin (m-β-CD) 1 : 1 host-guest compounds of methyl methacrylate (MMA) (1) or styrene (2) is described. The polymerization of complexes 1 a and 2 a was carried out in water with potassium peroxodisulfate (K2S2O8)/sodium hydrogensulfite (NaHSO3) as radical redox initiator at 60°C. Unthreading of m-β-CD during the polymerization led to water-insoluble poly(methyl methacrylate) (PMMA) (3) and polystyrene (4). By comparison, analogously prepared polymers from uncomplexed monomers 1 and 2 in ethanol as organic solvent with 2,2′-azoisobutyronitrile (AIBN) as radical initiator showed significantly lower molecular weights and were obtained in lower yields in all cases. Polymerization of m-β-CD complexed MMA in water, initiated with 2,2′-azobis(N,N ′-dimethyleneisobutyroamidine) dihydrochloride, occurred much faster than the polymerization of uncomplexed MMA in methanol under similar conditions. Furthermore, it was shown, that the precipitation polymerization of complexed MMA from homogeneous aqueous solution can be described by equations (Pn–1 ∝ lsqb;Irsqb;0.5) similar to those for classical polymerization in solution.
Solid mesoionic 2‐[2‐(isopropenylcarbonyloxy)ethylthio]‐1‐methyl‐6‐oxo‐3‐phenyl‐5‐propyl‐1,6‐dihydropyrimidin‐3‐ium‐4‐olate was complexed in water using β ‐cyclodextrin ( β ‐CD) and randomly methylated β ‐CD, which resulted in polymerizable complexes with 2:1 stoichiometry. The β ‐CD complex was characterized using ¹ H NMR, ROESY NMR and UV spectroscopy. Polymerization of the complex prepared from methylated β ‐CD led to a photosensitive polymer, which precipitated during polymerization and was nearly free of CD. Polymerization was carried out with a water‐soluble redox initiator. In addition, a copolymer with methyl methacrylate was prepared from the complexes, which showed a different mass‐dependent distribution in the incorporation in comparison to a copolymer prepared without CD in organic solvents.
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Novel functional polymers utilizing specific host/guest interactions were designed by introducing α-CD host molecules into poly(ε-lysine) chains as side groups. An interesting phase separation was observed as a result of the inclusion complexation between the polymeric host and 3-(trimethylsilyl)propionic acid as a model guest in aqueous media. This water-soluble polymeric host would be useful for various applications, particularly drug delivery, due to its biodegradability, low toxicity, and unique functionality represented as a complexation-induced phase separation.
Host‐guest complexes of styrene and randomly methylated β ‐cyclodextrin (m‐ β ‐CD) were polymerized in aqueous medium via the reversible addition fragmentation chain transfer (RAFT) process. 3‐Benzylsulfanylthiocarbonylsulfanylpropionic acid (TTC) was used as trithiocarbonate‐type RAFT agent. The results indicate a controlled character of the polymerization of the styrene complexes as the number‐average molecular weight, $\overline M _{\rm n}$ , increases linearly with monomer to polymer conversion; however, the molecular weights of the obtained polystyrenes deviate to higher values than those theoretically predicted. Nevertheless, the molecular weights can be controlled by variation of the initial RAFT agent concentration. The polystyrenes produced in this system exhibited narrower polydispersities (1.23 < $\overline M _{\rm w} /\overline M _{\rm n}$ < 2.36) than those produced without RAFT agent (5.24 < $\overline M _{\rm w} /\overline M _{\rm n}$ < 9.21) under similar conditions. The present contribution represents the first example of RAFT polymerization of a m‐ β ‐CD‐complexed hydrophobic vinylmonomer (styrene) from homogenous aqueous solution.
Schematic presentation of complexation and RAFT polymerization of m‐ β ‐CD‐complexed styrene with TTC as RAFT agent and evolution of the full molecular weight distributions in the CD‐mediated styrene free radical RAFT polymerization.
image Schematic presentation of complexation and RAFT polymerization of m‐ β ‐CD‐complexed styrene with TTC as RAFT agent and evolution of the full molecular weight distributions in the CD‐mediated styrene free radical RAFT polymerization.
An efficient synthesis of a cyclodextrin polymer by a polymer-analogous reaction of lithium β-cyclodextrinate with poly[(N-vinyl-2-pyrrolidinone)-co-(maleic anhydride)] is described. Because cyclodextrin polymer is highly water-soluble, its binding of guests, like 1-adamantanamine and l-adamantanecarboxylic acid, could be investigated by titration microcalorimetry. All cyclodextrin moieties are accessible by the guest within the polymer, but binding constants are slightly lower than those for native β-cyclodextrin. Binding constants are influenced by Coulomb interactions between the guest and the anionic polymer backbone.
A new method was developed to crosslink water‐soluble unsaturated polyester resins prepared from maleic anhydride and poly(ethylene glycol) in water as the solvent. Crosslinking was carried out with various molar ratios of the host‐guest complex consisting of styrene as the guest and methylated β ‐cyclodextrin as the host. Polymerizations were performed in water with K 2 S 2 O 8 /Na 2 S 2 O 5 as free radical initiator at 25 °C. Thermal properties of the networks obtained depend on the amount of styrene incorporated into the polymer.
Acceleration effect of me‐ β ‐CD during crosslinking of an unsaturated polyester with styrene in water: (a) monomer complexed with me‐ β ‐CD, and (b) with uncomplexed monomer.
magnified image Acceleration effect of me‐ β ‐CD during crosslinking of an unsaturated polyester with styrene in water: (a) monomer complexed with me‐ β ‐CD, and (b) with uncomplexed monomer.
We have successfully constructed a redox‐responsible hydrogel system by combination of β ‐cyclodextrin ( β ‐CD), dodecyl‐modified poly(acrylic acid) [p(AA/C 12 )], and a redox‐responsive guest, ferrocenecarboxylic acid (FCA). In the reduced state of FCA, the ternary mixture exhibited a gel‐like behavior, whereas, in its oxidized state, the mixture exhibited a sol behavior.
Conceptual illustration for the redox‐responsive hydrogel system.
magnified image Conceptual illustration for the redox‐responsive hydrogel system.
Original associating systems have been obtained by mixing hydrophobically end-capped polyethylene oxide and water soluble -cyclodextrin polymers in aqueous solutions. The hydrophobic ends of the PEO polymers, naphtyl and adamantyl groups, have been chosen in order to match the -cyclodextrin cavities. Inclusion complex formation between the PEO terminal groups and -cyclodextrin are at the origin of polymolecular associations. Complexation constants have been determined by fluorescence methods, using a fluorescent probe 1-8 ANS as a competitor for complexation against the adamantyl groups or directly checking the fluorescence of the naphtytl groups by fluorescence anisotropy measurements. The onsets of the polymolecular associations have been monitored by viscosimetry.
An original associating system is presented in this paper. It involves the mixing of two polymers: hydrophobically modified polyethylene oxide (PEO) and β-cyclodextrin copolymer. Inclusion complexes between the hydrophobic moieties (naphthalene or adamantane) and β-cyclodextrin cavities are at the origin of the attraction between the two polymers. The strength of the attractive interactions has been tailored by using different architectures for the amphiphilic polymer: linear or multi-arm branched PEO have been used, leading to a variable number of hydrophobic end-groups per chain. Interactions between the host and guest polymer have been demonstrated through both microscopic and macroscopic analysis of the properties of the medium: complexation constants have been determined by fluorescence methods and dialysis, while polymolecular associations have been evidenced by viscoelastic properties. Phase diagram studies have shown that the strength of the interactions between the two polymers is strongly related to the number of hydrophobic moieties per chain: while unmodified PEO and β-cyclodextrin copolymer are phase segregating, associative phase separations are observed for a number of hydrophobes per chain higher than or equal to three.
Efficient and practical methodology for the construction of carbohydrates, including oligosaccharide derivatives and sphingoglycolipids, was established on the basis of a water-soluble polymer supports having unique linkers that can be cleaved by specific conditions. Novel glycomonomers for the construction of polymer supports were synthesized and copolymerized with acrylamide to give three types of water-soluble glycopolymers having primer sugars through the specific linkers containing (i) p-substituted benzyl group, (ii) L-phenylalanine residue, and (iii) ceramide-mimetic L-serine derivative, respectively. These glycopolymers were employed for sugar elongation reactions with glycosyl transferases such as GlcNAc beta 1,4-galactosyl transferase, beta Gall-->3/4GlcNAc alpha-2,6-sialyl transferase, and beta Gall-->3/4GlcNAc alpha-2,3-sialyl transferase in the presence of each sugar nucleotide as glycosyl donor to afford polymers having N-acetyllactosamine, sialyl alpha-(2-->6) N-acetyllactosamine, and sialyl alpha-(2-->3) lactose residues in excellent yield. Subsequent hydrogenolysis, hydrolysis with alpha-chymotrypsin, or transglycosylation to ceramide with ceramide glycanase proceeds smoothly to give N-acetyllactosamine, a versatile sialyl alpha-(2-->6) N-acetyllactosamine derivative having a terminal amino group, and ganglioside GM3 in high yield.
Theophylline-polyrotaxane conjugates were synthesized by coupling theophylline with alpha-cyclodextrins (alpha-CDs) in the polyrotaxane. The polyrotaxane is a molecular assembly in which many alpha-CDs are threaded onto a poly(ethylene glycol) (PEG) chain capped with L-phenylalanine (L-Phe). Theophylline-7-acetic acid was activated by coupling with 4-nitrophenol, and then ethylenediamine was allowed to react with the active ester in order to obtain N-aminoethyl-theophylline-7-acetoamide. This derivative was coupled with a 4-nitrophenyl chloroformate-activated polyrotaxane to obtain the theophylline-polyrotaxane conjugates. The conjugates formed a specific association under physiological conditions, depending upon interactions between the theophylline molecules and/or the terminal l-Phe moiety in the conjugates. In vitro degradation of the conjugates revealed that theophylline-immobilized alpha-CDs were completely released by hydrolysis of the terminal peptide linkage in the polyrotaxane. This result indicates that the association of the conjugates does not induce the steric hindrance but rather enhances the accessibility of enzymes to the terminal peptide linkages. It is suggested that our designed drug-polyrotaxane conjugates can release the drugs via the dissociation of the supramolecular structure without steric hindrance of enzymatic accessibility to the terminal peptide linkages.
Parting the clouds: A supramolecular recognition reaction of cyclodexdrins with polymers - adamantyl derivative N-isopropylacrylamide copolymers - with inverse phase behavior is described. The turbidity of the polymer solutions depends upon the cyclodextrin concentration. Competition reactions with potassium-1-adamantylcarboxylate show that the inclusion-complex formation is reversible (see scheme).
To give pH sensitivity to a thermoreversible supramolecular-structured hydrogel system, poly(epsilon-lysine) (PL), as a cationic polymer, was grafted to dextran and used for inclusion complexation with alpha-cyclodextrins (alpha-CDs). The synthesized graft copolymer was characterized by 1H NMR spectroscopy, and the hydrogel formation was confirmed by X-ray diffraction and solid-state 13C NMR analysis. The hydrogelation was induced from a phase-separated structure of hydrated dextrans and hydrophobically aggregated inclusion complexes in buffer solution at pH 10.0. The prepared hydrogels showed thermoreversible gel-sol transitions as well as pH-sensitive phase transitions, which were recorded by the changes in UV/Vis transmittance. A rapid phase transition from gel to sol was observed upon decreasing the pH value to 4.0, which resulted from the dissociation process between the protonated guest polymer and alpha-CDs. The stimuli-responsive physical properties of the hydrogels were improved by modulating the degree of substitution of the grafted PL and the combination with alpha-CDs.
En route to intelligent hydrogels: Copolymers of N-isopropylacrylamide containing adamantyl groups can be cross-linked noncovalently with cyclodextrin dimers. This results in thermosensitive hydrogels with cloud points that are lower than those of the pure copolymers. Addition of monomeric methylated cyclodextrin results in an increase in the cloud points but has no significant influence on the viscosity of the copolymer solution. (Figure Presented)
Two polymeric substances, a poly{N-[tris(hydroxymethyl)methyl]acrylamide} (THMMA) substituted with adamantyl moieties and a beta-cyclodextrin/epichlorohydrin polycondensate, formed a host-guest type complex, which resulted in the gel formation upon mixing of these two compounds at appropriate conditions. Introduction of a drug molecule, i.e., naproxen, that was able to fill the beta-cyclodextrin cavities, thus expulsing adamantyl moieties, led to disruption of such association and inhibition of gel formation. The conditions required for the association of the two polymeric components and formation of the gel, as well as the dynamics of its inhibition by addition of naproxen was established. The procedure of using solutions of two associating polymers and an appropriate drug competitor can be used at targeted viscosupplementation.