Figure - available from: Drug Delivery
This content is subject to copyright. Terms and conditions apply.
(A) Response surface graph (3D) and contour graph showing the effect of the temperature (A) and concentration of SBE-β-CD (B), (B) the temperature (A) and inclusion time (C), (C) the concentration of SBE-β-CD (B) and inclusion time (C) added on the response (inclusion efficiency).
Source publication
Glaucocalyxin A (GLA), is a diterpenoid extracted from Hara and has been studied for decades for its diverse bioactivities. However, GLA presents poor solubility in water and low bioavailability through oral administration which has hindered its application in the clinic. So in this study, we prepared the inclusion complex of GLA in SBE-β-CD by ult...
Similar publications
A series of isoxazole linked to 4-(2-oxopyrrolinidyl-1)-tetrahydroquinoline derivatives was efficiently synthesized. The synthetic route started with the formation of the corresponding N-propargyl tetrahydroquinoline derivatives via cationic Povarov reaction. Tetrahydroquinoline-isoxazole hybrid systems (3a–p) were obtained with good yields (42–88%...
Citations
... The inclusion efficiency (IE) prepared at different conditions was analyzed by HPLC following a previous report with some modifications. 37 First, two of equal mass samples of OBB-HP-β-CD were precisely weighed on an analytical balance (20.00 mg). The samples were then fully dissolved in a fixed volume (5.00 mL) of either water or ethanol. ...
Propose
Oxyberberine (OBB), one of the main metabolites of berberine derived from intestinal and erythrocyte metabolism, exhibits appreciable anti-hyperuricemic activity. However, the low water solubility and poor plasma concentration–effect relationship of OBB hamper its development and utilization. Therefore, an OBB-hydroxypropyl-β-cyclodextrin (HP-β-CD) supersaturated drug delivery system (SDDS) was prepared and characterized in this work.
Methods
OBB-HP-β-CD SDDS was prepared using the ultrasonic-solvent evaporation method and characterized. Additionally, the in vitro and in vivo release experiments were conducted to assess the release kinetics of OBB-HP-β-CD SDDS. Subsequently, the therapeutic efficacy of OBB-HP-β-CD SDDS on hyperuricemia (HUA) was investigated by means of histopathological examination and evaluation of relevant biomarkers.
Results
The results of FT-IR, DSC, PXRD, NMR and molecular modeling showed that the crystallized form of OBB was transformed into an amorphous OBB-HP-β-CD complex. Dynamic light scattering indicated that this system was relatively stable and maintained by formation of nanoaggregates with an average diameter of 23 nm. The dissolution rate of OBB-HP-β-CD SDDS was about 5 times higher than that of OBB raw material. Furthermore, the AUC0-t of OBB-HP-β-CD SDDS (10.882 μg/mL*h) was significantly higher than that of the raw OBB counterpart (0.701 μg/mL*h). The oral relative bioavailability of OBB-HP-β-CD SDDS was also enhanced by 16 times compared to that of the raw material. Finally, in vivo pharmacodynamic assay showed the anti-hyperuricemic potency of OBB-HP-β-CD SDDS was approximately 5–10 times higher than that of OBB raw material.
Conclusion
Based on our findings above, OBB-HP-β-CD SDDS proved to be an excellent drug delivery system for increasing the solubility, dissolution, bioavailability, and anti-hyperuricemic potency of OBB.
... X 1 X 2 (X 1 X 3 , X 2 X 3 ) and X 12 (X 22 , X 32 ) represents the interaction and quadratic terms. [24] Three groups of parallel experiments were conducted, and the data were reported as mean � standard deviation (SD). Design Expert 13.0 (Stat-Ease, Inc., Minneapolis, Minnesota) was used to perform statistical analysis on the data through stepwise multiple regression to produce equations for optimization experimental conditions. ...
Berberine hydrochloride (BBH) is an isoquinoline alkaloid, and its diverse bioactivities have been studied for decades. However, BBH exhibits poor solubility and low oral bioavailability, which hampers its potential therapeutic exploitation. In this study, hydrosoluble Lysine‐modified β‐cyclodextrin (Lys‐β‐CD) was synthesized. Then BBH‐Lysine‐β‐cyclodextrin inclusion complexes (BBH/Lys‐β‐CD IC) were prepared by the co‐deposition method and optimized using the Box‐Behnken design. In addition, phase solubility was studied and showed that BBH and Lys‐β‐CD can form inclusion complexes in a stoichiometric ratio of 1 : 1. The morphological characterizations exhibited that the IC had an irregular sheet and layered structure. The results of FTIR and ¹H NMR revealed that BBH entered the Lys‐β‐CD cavity with non‐covalent interactions between host‐guest molecules. Furthermore, the binding pattern of BBH with the Lys‐β‐CD was investigated by molecular docking study. The release behavior of IC showed that BBH could be released slowly from the inclusion complex. Hence, the Lys‐β‐CD IC has broad application prospects in drug delivery and biomedical fields.
... The molecular docking study is used to predict the orientation of the guest within the host cavity. 54 The docking is carried out between GEM and β-CD by employing PyRx software. The chief docked configuration of the GEM-β-CD complex is represented in Figure 5 (a, side view; b, top view). ...
The toxicity of any drug against normal cells is a health hazard for all humans. At present, health and disease researchers from all over the world are trying to synthesize designer drugs with diminished toxicity and side effects. The purpose of the present study is to enhance the bioavailability and biocompatibility of gemcitabine (GEM) by decreasing its toxicity and reducing deamination during drug delivery by incorporating it inside the hydrophobic cavity of β-cyclodextrin (β-CD) without affecting the drug ability of the parent compound (GEM). The newly synthesized inclusion complex (IC) was characterized by different physical and spectroscopic techniques, thereby confirming the successful incorporation of the GEM molecule into the nanocage of β-CD. The molecular docking study revealed the orientation of the GEM molecule into the β-CD cavity (-5.40 kcal/mol) to be stably posed for ligand binding. Photostability studies confirmed that the inclusion of GEM using β-CD could lead to better stabilization of GEM (≥96%) for further optical and clinical applications. IC (GEM-β-CD) and GEM exhibited effective antibacterial and antiproliferative activities without being metabolized in a dose-dependent manner. The CT-DNA analysis showed sufficiently strong IC (GEM-β-CD) binding (Ka = 8.1575 × 1010), and this interaction suggests that IC (GEM-β-CD) may possibly exert its biological effects by targeting nucleic acids in the host cell. The newly synthesized biologically active IC (GEM-β-CD), a derivative of GEM, has pharmaceutical development potentiality.
... In the case of NFX/SBE-β-CD IC, drug solubility went from 263 ± 39 μg/mL (pH 1.2) to 338 ± 49 μg/mL (pH 5) and between 250 and 290 μg/mL for NFX/SBE-β-CD PM, indicating that the complex NFX/SBE-β-CD had increased the drug solubility in water in comparison with the raw NFX, particularly at pH 1. Similar results were described during the development of binary complexes of two polymorphs of mebendazole with β-CD [25]. On the other hand, the improvement of drug solubility from the corresponding PMs could be due, probably, to the formation of spherical particles (Fig. 4), and/or the incorporation of the drug into the cyclodextrins during the mixing process, as described in the literature [26][27][28]. was seen [19]. A broad absorption band centered around 3200 cm − 1 , with a small intensity peak at 1646 cm − 1 and a conjugation band at 2000 cm − 1 can be attributed to the stretching and bending of the hydrogen bond between O and H. ...
... As reported, the complexation of drugs by CDs can also be elucidated in solution using NMR spectroscopy, because it is possible to observe some modification of chemical shifts of the H and C atoms during host-guest interactions [26]. Changes in the chemical shift of specific nuclei provide information about interaction and the type of solid complex that it is formed (inclusion, partial, or non-inclusion) [41]. ...
... [59] Furthermore, increase in the anticancer activity of RH after complexation with α-CD is mainly due to the reason that α-CD can pass through the drug permeation barrier, called unstirred water layer (UWL) comprising of huge number of strong H-bond networks [60] by decreasing the effective thickness of the UWL. [61][62][63][64] ...
To increase the bioavailability of Rhodanine (RH), inclusion complexes (ICs) of RH with both α‐cyclodextrin (α‐CD) and β‐cyclodextrin (β‐CD) were prepared. The complexes were characterized by different physicochemical as well as spectroscopic techniques thereby indicating encapsulation of RH molecule into the cavities of α‐CD and β‐CD cavity. DSC analysis showed that the thermal stability of RH was enhanced after complexation. Computational study suggests the most preferred orientation of RH molecule within both CD cavities. In vitro antibacterial activity test illustrates that the IC2 RH‐α‐CD displayed better activity than pure RH and IC1 RH‐β‐CD. IC2 RH‐α‐CD (IC50=7.88 μM) shows the remarkable in vitro cytotoxic activity than pure RH (IC50=44 μM) and IC1 RH‐β‐CD towards human kidney cancer cell line (ACHN). Furthermore, interaction of RH, IC1 RH‐β‐CD and IC2 RH‐α‐CD with CT‐DNA was investigated and found that α‐CD enhances bioavailability of RH to greater extent compared to β‐CD. Additionally, photostability studies reveals that inclusion of RH using α‐CD induces better stabilization of RH as compared to β‐CD.
... The coefficient of the initial concentration of βCD (parameter Y) is the greatest in three independent parameters, showing the highest impact on the inclusion yield and squalene content compared to the parameters of inclusion time and the molar ratio. Similar results were obtained by Ren et al. [14] using Box- Behnken design to optimize the condition in preparation for the inclusion complex of Glaucocalyxin A sulfobutylether-βcyclodextrin. In both cases, the process variables of initial concentrations (Y), molar ratio (X), inclusion time (Z), and all interaction terms were significant model terms (p values < 0.05). ...
The present work aimed to investigate inclusion complexes of squalene with various cyclodextrins (native β-cyclodextrin and methyl-β-cyclodextrin). The production of squalene-β-cyclodextrin inclusion complex was obtained using Response Surface Methodology and obtained inclusion complexes were studied with FTIR spectroscopy, X-ray diffractometry, thermal analysis, and ¹H-NMR spectrometry. At the same time, squalene content was determined by reversed-phase high-performance liquid chromatography. All results confirmed that squalene was successfully involved in the cyclodextrin cavities. Optimizing the condition in preparation for the squalen-β-cyclodextrin inclusion complex yielded 54.3% with squalene content of 9.01%. The essential difference for the inclusion complex of squalene with methylated beta-cyclodextrin was that no precipitate formed in the initial mixture, and the complex was more efficiently dispersed in water. The conclusions of the inclusion complex formation were confirmed by computer simulation by optimizing the complex geometry using the DFT, MM2, and MP3 methods.
... The plate was slowly shaken at room temperature for 10 min. Then the absorbance of the DMSO-cell solution was detected by ELISA Reader at 490 nm [25]. The detection was performed in parallel 3 times, and the average value was used to calculate the cell viability. ...
Benzyl isothiocyanate (BITC) is widely utilized in multiple biomedical fields, due to its significant antibacterial properties and low toxicity. However, poor water solubility and pungent odor has limited its application in the food industry. In this study, we first prepared inclusion complexes of BITC in GLU-β-CD and HP-β-CD using ultrasound, which is able to overcome the hindrance of poor water solubility and high volatility. Then, the BITC-β-CD inclusion complexes were characterized by using high-performance liquid chromatography (HPLC), nuclear magnetic resonance hydrogen spectra (1H-NMR), infrared absorption spectra (IR), and differential scanning calorimetry (DSC) to confirm their stability. Further, the evaluation of antibacterial and antitumor effects of the BITC-β-CD inclusion complexes showed that they had great bactericidal activity against both Escherichia coli and Staphylococcus aureus cells, and also inhibited the growth of HepG2 cells in vitro. In addition, our results indicated that BITC-β-CD complexes were able to inhibit the growth of S. aureus in broccoli juice and extend the shelf life of broccoli juice, demonstrating the potential of β-cyclodextrin to improve the stability and controlled release of BITC. Taken together, our results show that BITC-β-CD complexes have good potential for application in the food industry.
... SBE-β-CD has widely been explored by formulating ICs to improve the solubility and dissolution profiles of several hydrophobic compounds viz. honokiol (Xu et al., 2014), curcumin (Cutrignelli et al., 2014), chrysin (CHR) (Kulkarni & Belgamwar, 2017), glaucocalyxin A (Ren et al., 2019), thalidomide (Kale et al., 2008), and so on. In addition, few SBE-β-CD ICs-based nanoparticles (NPs) have also been reported. ...
... Similarly, several studies demonstrated the effectiveness of SBE-β-CD-based ICs for the delivery of various anticancer drugs viz. docetaxel (Ren et al., 2020;Sadaquat & Akhtar, 2020), glaucocalyxin A (Ren et al., 2019), fisetin (Mohtar et al., 2017), erlotinib (Erlo) (Devasari et al., 2015), honokiol (Xu et al., 2014), curcumin (Cutrignelli et al., 2014), thalidomide (Kale et al., 2008), and gemcitabine (Rescifina et al., 2019). ...
Sulfobutylether β-cyclodextrin (SBE-β-CD) is a polyanionic cyclic oligosaccharide that contains glucopyranose units forming a torus ring-like structure. SBE-β-CD is gifted with many favorable properties viz. relatively high solubility (>50 folds compared to β-CD), improved stability, and biocompatibility that praised SBE-β-CD as a smart polymer for drug delivery applications. Commercially, SBE-β-CD is popular by its brand name Captisol®. The present review discusses the structure, properties, and preparation methods of SBE-β-CD-based inclusion complexes (ICs). Furthermore, we discuss here the preparation and applications of SBE-β-CD ICs-based nanoparticulate drug delivery systems, which combines the merits of both, ICs (enhanced solubility) and nanoparticles (NPs, targeted therapy). Patents on and FDA-approved Captisol®-enabled products are tabulated in the benefit of readers. The toxicological aspects and current clinical status of SBE-β-CD or SBE-β-CD-based products are briefly explained in the present review. In our opinion, the present review would be a pathfinder to allow dissemination of information on SBE-β-CD.
... Hence, complexation of TCP with -CD was found to improve the anticancer activity of TCP towards ACHN cells. This may be probably due to the sustained release of TCP from the microsphere of -CD, which leads to greater bioavailability thus enhancing the drug effect ( Ren et al., 2019 ). In addition, the anticancer activity enhancement of TCP by complexation with -CD is also likely due to the reason that -CD can infiltrate into the drug permeation barrier, called unstirred water layer (UWL) consisting of a large number of strong H-bond networks, better than the free form of TCP ( Loftsson, 2012 ). ...
We aim to develop the complex of ticlopidine hydrochloride (TCP) with β-cyclodextrin (β-CD) and to investigate its antibacterial and cytotoxic activities. The complex was characterized by various physicochemical as well as spectroscopic techniques suggesting the successful inclusion of TCP molecule into the β-CD cavity. TG analysis showed that the thermal stability of TCP was found to improve after complexation. Molecular docking study speculated the most preferred orientation of TCP molecule within the binding pocket of β-CD cavity. In vitro antibacterial activity test demonstrated that the TCP-β-CD complex displayed better activity than pure TCP. TCP-β-CD complex (IC50 = 24 μM) also exhibited significant in vitro cytotoxic activity than pure TCP (IC50 = 44 μM) towards human kidney cancer cell line (ACHN). Furthermore, the complex induces the ROS generation in ACHN cells more pronouncedly than TCP alone, suggesting the increased apoptotic activity of TCP after complexation. These results reveals that inclusion of TCP using β-CD could lead to stabilization of TCP and efficient display of its antibacterial and cytotoxic activities.
... Therefore, it is of great value to study novel GLA derivatives with good biological activities. [16][17] Figure 1 Structures of representative natural products with exomethylene cyclopentanone on the D-ring In our previous study, a novel ent-kaurene diterpenoid compound glaucocalyxin H (GLH, Figure 1), acetylated product of protocatechualdehyde and 7,14-hydroxy group of GLA, was isolated from the traditional Chinese herb Isodon glaucocalyx (maxin) Hara. [15] Bioactivity study showed GLH exhibited higher inhibitory activities than GLA against EC-1, U87, A549, MCF-7, Hela cells, Hep G2 and K562 cell lines. ...
