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Fourier transform infrared spectroscopy (FTIR) spectra of RES, two different samples of TPGS and of the RES-TPGS formulations prepared (a); magnification of a significant spectral region (b).
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Children affected by chronic liver disease exhibit impaired neurocognitive development and growth due to the low absorption and digestion of nutrients. Furthermore, malnutrition is an adverse prognostic factor in liver transplantation as it is associated with an increase in morbidity and mortality. D-α-tocopheryl-polyethylene-glycol-succinate (TPGS...
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Context 1
... this work, the FTIR analyses were carried out on individual components (RES and TPGS), and on lyophilized RES-TPGSs having different RES:TPGS (w/w) ratios, to qualitatively evaluate the success of the encapsulation reaction. Figure 4a shows the FTIR spectra of RES, TPGS, and of RES-TPGS samples containing RES and TPGS in 1:1-1:7 (w/w) ratios, whereas Figure 4b shows a significant region of the spectra of the formulations, where typical signals of RES are detectable. ...
Context 2
... this work, the FTIR analyses were carried out on individual components (RES and TPGS), and on lyophilized RES-TPGSs having different RES:TPGS (w/w) ratios, to qualitatively evaluate the success of the encapsulation reaction. Figure 4a shows the FTIR spectra of RES, TPGS, and of RES-TPGS samples containing RES and TPGS in 1:1-1:7 (w/w) ratios, whereas Figure 4b shows a significant region of the spectra of the formulations, where typical signals of RES are detectable. ...
Citations
... VES-GEM is overall an amphiphilic molecule in which the VES aliphatic tail contained in the lipidic portion is hydrophobic, whilst the GEM portion is more polar and contains -OH, -F, and -NH2 groups [72]. The lipophilic moiety of the VES-GEM conjugate prodrug system may allow successful encapsulation in the hydrophobic core of the Pluronic ® micelles by conferring hydrophobicity and also additional antioxidant and anticancer properties. ...
Pancreatic cancer (PC) is an aggressive cancer subtype presenting unmet clinical challenges. Conventional chemotherapy, which includes antimetabolite gemcitabine (GEM), is seriously undermined by a short half-life, its lack of targeting ability, and systemic toxicity. GEM incorporation in self-assembled nanosystems is still underexplored due to GEM’s hydrophilicity which hinders efficient encapsulation. We hypothesized that vitamin E succinate–GEM prodrug (VES-GEM conjugate) combines hydrophobicity and multifunctionalities that can facilitate the development of Pluronic®F68 and Pluronic®F127 micelle-based nanocarriers, improving the therapeutic potential of GEM. Pluronic®F68/VES-GEM and Pluronic®F127/VES-GEM micelles covering a wide range of molar ratios were prepared by solvent evaporation applying different purification methods, and characterized regarding size, charge, polydispersity index, morphology, and encapsulation. Moreover, the effect of sonication and ultrasonication and the influence of a co-surfactant were explored together with drug release, stability, blood compatibility, efficacy against tumour cells, and cell uptake. The VES-GEM conjugate-loaded micelles showed acceptable size and high encapsulation efficiency (>95%) following an excipient reduction rationale. Pluronic®F127/VES-GEM micelles evidenced a superior VES-GEM release profile (cumulative release > 50%, pH = 7.4), stability, cell growth inhibition (<50% cell viability for 100 μM VES-GEM), blood compatibility, and extensive cell
internalization, and therefore represent a promising approach to leveraging the efficacy and safety of GEM for PC-targeted therapies.
... Through a phase-solubility analysis, the researchers determined that TPGS was suitable for encapsulating resveratrol in micelles; next, resveratrol TPGS formulations were made through solvent casting and solvent diffusion evaporation. Low polydispersity, a somewhat neutral Zeta potential, and small mean diameters (12 nm) were all characteristics of resveratrol TPGS colloidal dispersions [159]. Infrared spectroscopy and differential scanning calorimetry both validated the formulations' strong drug loading capacity and stable drug release. ...
... Resveratrol TPGSs showed reduced toxicity on HaCaT cells compared to empty TPGSs while maintaining the same level of antioxidant activity as pure resveratrol as measured by the DPPH assay. The antioxidant activity of resveratrol and the reduced surfactant toxicity on normal cells suggest that resveratrol TPGS micelles may be able to overcome the obstacles of conventional liver disease therapy [159,160]. Table 3 details the encouraging results obtained from a variety of nanoformulation methods for increasing resveratrol's biological activity. Table 3. ...
Resveratrol is a stilbenoid from red grapes that possesses a strong antioxidant activity. Resveratrol has been shown to have anticancer activity, making it a promising drug for the treatment and prevention of numerous cancers. Several in vitro and in vivo investigations have validated resveratrol’s anticancer capabilities, demonstrating its ability to block all steps of carcinogenesis (such as initiation, promotion, and progression). Additionally, resveratrol has been found to have auxiliary pharmacological effects such as anti-inflammatory, cardioprotective, and neuroprotective activity. Despite its pharmacological properties, several obstacles, such as resveratrol’s poor solubility and bioavailability, as well as its adverse effects, continue to be key obstacles to drug development. This review critically evaluates the clinical trials to date and aims to develop a framework to develop resveratrol into a clinically viable drug.
... A study showed that formulations containing TPGS and resveratrol, a natural non-flavonoid polyphenol with diverse biological activities, sustained drug release, and good drug-loading capacities. TPGS, as a host of poorly soluble compounds, ameliorated the water solubility of resveratrol and reduced its intrinsic cytotoxic effects [84]. Resveratrol is effectively loaded in the TPGS nanoemulsions, and their loading efficiencies were found to be 99.38% ...
Tocotrienols have higher medicinal value, with multiple sources of evidence showing their biological properties as antioxidant, anti-inflammatory, and osteoprotective compounds. However, tocotrienol bioavailability presents an ongoing challenge in its translation into viable products. This is because tocotrienol oil is known to be a poorly water-soluble compound, making it difficult to be absorbed into the body and resulting in less effectiveness. With the potential and benefits of tocotrienol, new strategies to increase the bioavailability and efficacy of poorly absorbed tocotrienol are required when administered orally. One of the proposed formulation techniques was self-emulsification, which has proven its capacity to improve oral drug delivery of poorly water-soluble drugs by advancing the solubility and bioavailability of these active compounds. This review discusses the updated evidence on the bioavailability of tocotrienols formulated with self-emulsifying drug delivery systems (SEDDSs) from in vivo and human studies. In short, SEDDSs formulation enhances the solubility and passive permeability of tocotrienol, thus improving its oral bioavailability and biological actions. This increases its medicinal and commercial value. Furthermore, the self-emulsifying formulation presents a useful dosage form that is absorbed in vivo independent of dietary fats with consistent and enhanced levels of tocotrienol isomers. Therefore, a lipid-based formulation technique can provide an additional detailed understanding of the oral bioavailability of tocotrienols.
... To overcome the aforementioned problems and to allow the exploitation of PHYs as health enhancers, researchers increasingly resort to nanotechnology and nanostructures with dimensions of nanometers (nm). Over the years, several PHY-enriched nanomaterials have been engineered to overcome the poor solubility, permeability, and negative pharmacokinetics of PHYs, and different nanosized delivery systems (DSs) to transport therapeutic concentrations of PHYs to their targets have been designed [12,14]. Moreover, aiming at the better treatment of diseases, such as cancer, using PHYs, novel nanotechnological carriers for the codelivery of PHYs and conventional anticancer drugs have been developed with various benefits, including improved solubility, reduced adverse effects, higher efficacy, reduced dose, improved dosing frequency, reduced drug resistance, improved bioavailability, and higher patient compliance [15]. ...
The awareness of the existence of plant bioactive compounds, namely, phytochemicals (PHYs), with health properties is progressively expanding. Therefore, their massive introduction in the normal diet and in food supplements and their use as natural therapeutics to treat several diseases are increasingly emphasized by several sectors. In particular, most PHYs possessing antifungal, antiviral, anti-inflammatory, antibacterial, antiulcer, anti-cholesterol, hypoglycemic, immunomodulatory, and antioxidant properties have been isolated from plants. Additionally, their secondary modification with new functionalities to further improve their intrinsic beneficial effects has been extensively investigated. Unfortunately, although the idea of exploiting PHYs as therapeutics is amazing, its realization is far from simple, and the possibility of employing them as efficient clinically administrable drugs is almost utopic. Most PHYs are insoluble in water, and, especially when introduced orally, they hardly manage to pass through physiological barriers and scarcely reach the site of action in therapeutic concentrations. Their degradation by enzymatic and microbial digestion, as well as their rapid metabolism and excretion, strongly limits their in vivo activity. To overcome these drawbacks, several nanotechnological approaches have been used, and many nanosized PHY-loaded delivery systems have been developed. This paper, by reporting various case studies, reviews the foremost nanosuspension- and nanoemulsion-based techniques developed for formulating the most relevant PHYs into more bioavailable nanoparticles (NPs) that are suitable or promising for clinical application, mainly by oral administration. In addition, the acute and chronic toxic effects due to exposure to NPs reported so far, the possible nanotoxicity that could result from their massive employment, and ongoing actions to improve knowledge in this field are discussed. The state of the art concerning the actual clinical application of both PHYs and the nanotechnologically engineered PHYs is also reviewed.
... Anyway, to overcome the afore-mentioned problems and to allow the exploitation of PHYs as health enhancers, researchers increasingly resort to nanotechnology and nanostructures with dimensions of nanometers (nm). In the years, several PHYs-enriched nanomaterials have been engineered to overcome the poor solubility, permeability, and negative pharmacokinetics of PHYs, and different nanosized delivery systems (DSs)to transport therapeutic concentrations of PHYs to the targets have been developed [12,14]. ...
The awareness of the existence in plants of bioactive compounds namely phytochemicals (PHYs), having health properties is progressively expanding. Therefore, their massive introduction in the normal diet, in food supplements, and their use as natural therapeutics to treat several diseases are increasingly emphasized by several sectors. Particularly, most PHYs possessing antifungal, antiviral, anti-inflammatory, antibacterial, antiulcer, anti-cholesterol, hypoglycemic, immunomodulatory, and antioxidant properties have been isolated from plants. Additionally, their secondary modification with new functionalities, to further improve their intrinsic beneficial effects, is extensively investigated. Unfortunately, although the idea of exploiting PHYs as therapeutics is amazing, its realization is far from simple, and the possibility of exploiting them as effective orally administrable drugs is almost utopic. Most PHYs are insoluble in water and, when introduced orally, they scarcely reach the site of action in therapeutic concentrations. Degradation by enzymatic and microbial digestion, occurring in the mouth, stomach, and intestine, as well as fast metabolism and rapid excretion via the kidney, biliary, or lung, strongly limit their in vivo activity. To overcome these drawbacks, several nanotechnological approaches have been used and many PHYs-loaded delivery systems with dimensions of nanometers have been developed. This paper, also by reporting various recent case studies, reviews the foremost nano-suspension and nano-emulsion-based techniques developed for formulating the most relevant PHYs in more bioavailable nanoparticles (NPs), suitable or promising for clinical application. Also, the acute and chronic toxic effects due to the exposure to NPs reported so far, the possible nanotoxicity which could derive by their massive employment, as well as the ongoing actions to improve the knowledge in the field were discussed. The state of the art concerning the actual clinical application of both PHYs and the nanotechnologically engineered PHYs was also reviewed.
... TP is generally used as a functional unit to form polymeric nanocarriers in drug delivery systems [23,24] or in wound dressings [25] because of its great antioxidant activity. Some water-soluble forms of TP (such as D-α-tocopheryl-polyethylene-glycol-succinate-vitamin E TPGS) are employed also as solubilizing agent for lipophilic drugs (retinoic acid, paclitaxel, and resveratrol) [26,27]. In addition to pharmacological use, TP is widely used in the cosmetology and food industries [28]. ...
Water-soluble forms of α-tocopherol (TP) as an effective antioxidant were obtained by encapsulating it into nanoparticles (NPs) of amphiphilic copolymers of N-vinylpyrrolidone with triethylene glycol dimethacrylate (CPL1-TP) and N-vinylpyrrolidone with hexyl methacrylate and triethylene glycol dimethacrylate (CPL2-TP) synthesized by radical copolymerization in toluene. The hydrodynamic radii of NPs loaded with TP (3.7 wt% per copolymers) were typically ca. 50 or 80 nm depending on copolymer composition, media, and temperature. Characterization of NPs was accomplished by transmission electron microscopy (TEM), IR-, and 1H NMR spectroscopy. Quantum chemical modeling showed that TP molecules are capable to form hydrogen bonds with donor groups of the copolymer units. High antioxidant activity of both obtained forms of TP has been found by the thiobarbituric acid reactive species and chemiluminescence assays. CPL1-TP and CPL2-TP effectively inhibited the process of spontaneous lipid peroxidation as well as α-tocopherol itself. The IC50 values of luminol chemiluminescence inhibition were determined. Antiglycation activity against vesperlysine and pentosidine-like AGEs of TP water-soluble forms was shown. The developed NPs of TP are promising as materials with antioxidant and antiglycation activity and can be used in various biomedical applications.
... The Res-NLPs were more cytotoxic than the blank NLPs within the lipid concentration range of 350~1400 μM. This result indicates high levels of Res encapsulated in high concentrations of Res-NLPs are toxic to cells, while low concentrations of Res are not [33,34]. Furthermore, above 80% cell viability was observed in all three types of cells treated with the blank NLPs at high lipid concentrations (350~700 μM), suggesting the good cell safety of the materials utilized for NLPs preparation. ...
... The Res-NLPs were more cytotoxic than the blank NLPs within the lipid concentration range of 350~1400 µM. This result indicates high levels of Res encapsulated in high concentrations of Res-NLPs are toxic to cells, while low concentrations of Res are not [33,34]. Furthermore, above 80% cell viability was observed in all three types of cells treated with the blank NLPs at high lipid concentrations (350~700 µM), suggesting the good cell safety of the materials utilized for NLPs preparation. ...
Due to the stratum corneum barrier, resveratrol is difficult to be absorbed transdermally, limiting its anti-aging and skin-brightening effects. Furthermore, there is a lack of systematic studies on the efficacy of resveratrol in human skin, especially in three-dimensional skin models and clinical trials. To overcome the low transdermal delivery issue, we encapsulated resveratrol into nanoliposomes using the high-pressure homogenization method to develop an efficient transdermal drug delivery system, and systematically evaluated its anti-aging and skin-brightening efficacy via cell line models, a three-dimensional skin model and human skin. The resveratrol nanoliposomes effectively improved the transdermal penetration and retention of resveratrol and enhanced cellular uptake. In addition, compared to free resveratrol, resveratrol nanoliposomes remarkably enhanced the skin-care effects by promoting the antioxidant capacity and collagen synthesis, inhibiting the secretion of matrix metalloproteinases, tyrosine activity and melanin synthesis. Notably, human clinical trials proved the anti-wrinkle and skin-brightening effectiveness of resveratrol nanoliposomes. Three levels of systematic studies indicated that resveratrol nanoliposomes could be a promising transdermal drug delivery system to enhance the anti-aging and skin-brightening effects of resveratrol.
... As observable in Figure 6a, the weight loss was almost quantitative (94%) for both R1HG and R2HG, and the equilibrium was reached after either 6 h 45 min (R1) or 5 h 45 min (R2). To know exactly the kinetics and the main mechanisms that governed the loss of water from the R1HG and R2HG, we fit the data of the curves in Figure 6a with the zero order model (% cumulative water release vs. time), first-order model (Log10 % cumulative water residuals vs. time), Hixson-Crowell model (cube root of % cumulative water residuals vs. time), Higuchi model (% cumulative water release vs. square root of time), and Korsmeyer-Peppas model (Ln% cumulative water release vs. Ln of time) [37,[46][47][48][49]. The kinetic models were so obtained as dispersion graphs, and the coefficients of determination (R 2 ) of the linear regressions of the obtained dispersion graphs were the parameters to determine which model best fit the water release data. ...
... R 2 values are reported in Table 2 and proved that the water loss from R1HG best fit with the first-order As observable in Figure 6a, the weight loss was almost quantitative (94%) for both R1HG and R2HG, and the equilibrium was reached after either 6 h 45 min (R1) or 5 h 45 min (R2). To know exactly the kinetics and the main mechanisms that governed the loss of water from the R1HG and R2HG, we fit the data of the curves in Figure 6a with the zero order model (% cumulative water release vs. time), first-order model (Log 10 % cumulative water residuals vs. time), Hixson-Crowell model (cube root of % cumulative water residuals vs. time), Higuchi model (% cumulative water release vs. square root of time), and Korsmeyer-Peppas model (Ln% cumulative water release vs. Ln of time) [37,[46][47][48][49]. The kinetic models were so obtained as dispersion graphs, and the coefficients of determination (R 2 ) of the linear regressions of the obtained dispersion graphs were the parameters to determine which model best fit the water release data. ...
Water pollution from dyes is harmful to the environment, plants, animals, and humans and is one of the most widespread problems afflicting people throughout the world. Adsorption is a widely used method to remove contaminants derived from the textile industry, food colorants, printing, and cosmetic manufacturing from water. Here, aiming to develop new low-cost and up-scalable adsorbent materials for anionic dye remediation and water decontamination by electrostatic interactions, two cationic resins (R1 and R2) were prepared. In particular, they were obtained by copolymerizing 4-ammonium methyl and ethyl styrene monomers (M1 and M2) with dimethylacrylamide (DMAA), using N-(2-acryloylamino-ethyl)-acrylamide (AAEA) as cross-linker. Once characterized by several analytical techniques, upon their dispersion in an excess of water, R1 and R2 provided the R1- and R2-based hydrogels (namely R1HG and R2HG) with equilibrium degrees of swelling (EDS) of 900% and 1000% and equilibrium water contents (EWC) of 90 and 91%, respectively. By applying Cross’ rheology equation to the data of R1HG and R2HG’s viscosity vs. shear rate, it was established that both hydrogels are shear thinning fluids with pseudoplastic/Bingham plastic behavior depending on share rate. The equivalents of -NH3+ groups, essential for the electrostatic-based absorbent activity, were estimated by the method of Gaur and Gupta on R1 and R2 and by potentiometric titrations on R1HG and R2HG. In absorption experiments in bulk, R1HG and R2HG showed high removal efficiency (97–100%) towards methyl orange (MO) azo dye, fluorescein (F), and their mixture (MOF). Using F or MO solutions (pH = 7.5, room temperature), the maximum absorption was 47.8 mg/g in 90′ (F) and 47.7 mg/g in 120′ (MO) for R1, while that of R2 was 49.0 mg/g in 20′ (F) and 48.5 mg/g in 30′ (MO). Additionally, R1HG and R2HG-based columns, mimicking decontamination systems by filtration, were capable of removing MO, F, and MOF from water with a 100% removal efficiency, in different conditions of use. R1HG and R2HG represent low-cost and up-scalable column packing materials that are promising for application in industrial wastewater treatment.
... Based on these results, it can be assumed that the weight loss is not influenced neither by the initial amount of gel, nor by the material of the container. To exactly know the kinetics and the main mechanisms that govern the loss of water from CP1_1.1-Hgel, the data of both curves in Figure 6a were fit with the zero order model (% cumulative water release vs. time), first-order model (Log10 of % cumulative water remaining vs. time), Hixson-Crowell model (cube root of % cumulative water remaining vs. time), Higuchi model (% cumulative water release vs. square root of time), and Korsmeyer-Peppas model (Ln of % cumulative water release vs. Ln of time) obtaining the related dispersion graphs [40][41][42][43]. The highest value of the coefficient of determination (R 2 ) of the equations of the linear regressions of these graphs was considered as the parameter for determining which model best fits the water release data. ...
Objects touched by patients and healthcare workers in hospitals may harbor pathogens, including multi-drug resistant (MDR) staphylococci, enterococci (VRE), Escherichia coli, Acinetobacter, and Pseudomonas species. Medical devices contaminated by these pathogens may also act as a source of severe and difficult-to-treat human infections, thus becoming a critical public health concern requiring urgent resolutions. To this end, we recently reported the bactericidal effects of a cationic copolymer (CP1). Here, aiming at developing a bactericidal formulation possibly to be used either for surfaces disinfection or to treat skin infections, CP1 was formulated as a hydrogel (CP1_1.1-Hgel). Importantly, even if not cross-linked, CP1 formed the gel upon simple dispersion in water, without requiring gelling agents or other additives which could be skin-incompatible or interfere with CP1 bactericidal effects in possible future topical applications. CP1_1.1-Hgel was characterized by attenuated-total-reflectance Fourier transform infrared (ATR-FTIR) and UV-Vis spectroscopy, as well as optic and scanning electron microscopy (OM and SEM) to investigate its chemical structure and morphology. Its stability was assessed by monitoring its inversion properties over time at room temperature, while its mechanical characteristics were assessed by rheological experiments. Dose-dependent cytotoxicity studies performed on human fibroblasts for 24 h with gel samples obtained by diluting CP_1.1-Hgel at properly selected concentrations established that the 3D network formation did not significantly affect the cytotoxic profile of CP1. Also, microbiologic investigations carried out on two-fold serial dilutions of CP1-gel confirmed the minimum inhibitory concentrations (MICs) previously reported for the not formulated CP1.Selectivity indices values up to 12 were estimated by the values of LD50 and MICs determined here on gel samples.
... Probably, due to the much higher concentration of the cationic macromolecules in the gel, more hydrogen bonds between the water and heteroatoms present in the copolymer structure were possible, thus causing a higher retention of water. To exactly know the main mechanisms that govern the loss of water from the CP1OP2-Hgel, the data of the curve in Figure 9a were fit with several mathematical kinetic models as reported in other published studies [44][45][46][47], obtaining the related dispersion graphs. The mathematical model which provided the graph, whose linear tendency line (supplied by Microsoft Excel software using the least-squares method) had the highest value of the coefficient of determination (R 2 ) was selected as that which best fit the water release data. ...
Here, a new two-component hydrogel (CP1OP2-Hgel) was developed, simply by dispersing in water two cationic bactericidal polymers (CP1 and OP2) effective against several multidrug-resistant (MDR) clinical isolates of the most relevant Gram-positive and Gram-negative species. Interestingly, while OP2 acts only as an antibacterial ingredient when in gel, CP1 works as both an antibacterial and a gelling agent. To verify whether it would be worthwhile to use CP1 and OP2 as bioactive ingredients of a new hydrogel supposed for a future treatment of skin infections, dose-dependent cytotoxicity studies with CP1 and OP2 were performed on human fibroblasts for 24 h, before preparing the formulation. Although a significant cytotoxicity at concentrations > 2 µM was evidenced for both polymers, selectivity indices (SIs) over 12 (CP1) and up to six (OP2) were determined, due to the powerful antibacterial properties of the two polymers, thus supporting the rationale for their formulation as a hydrogel. The chemical structure and morphology of CP1OP2-Hgel were investigated by PCA-assisted attenuated total reflectance (ATR) Fourier-transform infrared (FTIR) analysis and scanning electron microscopy (SEM), while its rheological properties were assessed by determining its dynamic viscosity. The cumulative weight loss and swelling percentage curves, the porosity, and the maximum swelling capability of CP1OP2-Hgel were also determined and reported. Overall, due to the potent bactericidal effects of CP1 and OP2 and their favorable selectivity indices against several MDR pathogens, good rheological properties, high porosity, and strong swelling capability, CP1OP2-Hgel may, in the future, become a new weapon for treating severe nosocomial skin infections or infected chronic wounds. Further investigations in this sense are currently being carried out.
