Formulation of Apigenin-Cyclodextrin-Chitosan Ternary Complex: Physicochemical Characterization, In Vitro and In Vivo Studies.

The current investigation was performed with an aim to improve the aqueous solubility, dissolution rate, and thus the biological activity of apigenin (APG) using the solubilizers hydroxypropyl beta-cyclodextrin (HPßCD) and chitosan (CTSN). A binary and ternary inclusion complexes of APG with HPßCD and CTSN were prepared by physical mixing, fusion, and solvent evaporation methods. The liquid state characterization of the APG, the solubilizers, and the physical and chemical interactions between them was done through phase solubility approach. The solid-state characterization was performed by proton nuclear magnetic resonance (1H-NMR), differential scanning calorimetry (DSC), and X-ray diffractometry (XRD). The in vitro dissolution test and antioxidant activity and in vivo anti-inflammatory activity of the ternary inclusion complex in albino rats were performed to assess the performance of the APG. Phase solubility study results revealed a remarkable increase in apparent stability constant (Kc) and complexation efficiency (CE) of HPßCD in presence of CTSN in ternary complex with above 8 folds more increment in solubility of APG than its binary complex. The in vitro dissolution rate, antioxidant activity, and the anti-inflammatory effect of the APG ternary inclusion complex were found to be significantly higher than that of pure APG. Solid state characterization confirmed the formation of a ternary inclusion complex. 1H-NMR study gave more insight at molecular level into how different groups of APG were responsible for complex formation with the HPßCD and how CTSN was significantly influencing on the APG-HPßCD complex formed. Nevertheless, pharmacokinetic and histopathological studies of our APG-HPßCD-CTSN ternary complex would yield much rewarding results.

Formulation of Curcumin-ß-cyclodextrin-polyvinylpyrrolidone supramolecular inclusion complex: experimental, molecular docking, and preclinical anti-inflammatory assessment.

This research planned to ameliorate an aqueous solubility and dissolution of Curcumin (CUR) by the formulation of inclusion complex with ß-cyclodextrin (ß-CD) and polyvinylpyrrolidone (PVP). The phase solubility study was performed to assess the solubility of CUR. The prepared CUR complex assessed for dissolution study, physicochemical evaluation, in-vitro antioxidant activity, molecular modeling, and anti-inflammatory assessment. The pivotal findings of phase-solubility studies demonstrate apparent stability constant (Kc) and complexation efficiency (CE) values for CUR-ß-CD and CUR-ß-CD-PVP complex was 175.4 M -1, 1.15% and 833.3.2 M -1 and 5.21%, respectively. The characterization results revealed amorphization of crystalline state (CUR) into amorphous state. The maximum drug release found with the ternary CUR complex (F7), i.e. 45.41 ± 3.78% in 6 h study. The chemical shift in the NMR supports that the aromatic ring of CUR is completely complexed inside the ß-CD cavity. The antioxidant activity of pure CUR was found to be 58.02 ± 2.21% and CUR ternary complex (F7) showed significantly higher activity to 96.02 ± 2.46%. The in-vivo effect of CUR complex (F7) was also found significantly higher than that of pure CUR. The molecular modeling study depicted that PVP increased the stability of the ternary complex by forming the link between CUR and ß-CD. Thus, the ternary inclusion complex of CUR-ß-CD-PVP could contribute as an innovative outcome in the enhancement of solubility and in-vivo activity.

Preparation of novel S-allyl cysteine chitosan based nanoparticles for use in ischemic brain treatment.

Objective: To enhance the brain bioavailability of S-allyl-l-cysteine (SC) by developing novel S-allyl-l-cysteine chitosan nanoparticles (SC CS NPs) and examining the quantity of SC by developing a novel method of ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) in ischemic rat brain treatment. Methods: The ionotropic gelation method was used to develop S-allyl cysteine-loaded CS NPs. The 4-factor, 5-level central composite design was optimized to determine the effect of independent variables, i.e., particle size, polydispersity index (PDI), zeta potential, EE, and loading capacity, together with their characterization, followed by drug release and intranasal permeation to enhance the brain bioavailability and examination of their neurobehavioral and biochemical parameters with their histopathological examination. Results: SC CS NPs were optimized at the particle size of 93.21 ± 3.31 nm (PDI: 0.317 ± 0.003), zeta potential of 44.4 ± 2.93, and drug loading of 41.23 ± 1.97% with an entrapment efficiency of 82.61 ± 4.93% having sustain and controlled release (79.92 ± 3.86%) with great permeation (>80.0%) of SC. SC showed the retention time of 1.021 min and 162.50/73.05 m/z. SC showed good linearity in the range of 5.0-1300.0 ng mL-1, % inter-and-intraday accuracy of 96.00-99.06% and CV of 4.38-4.38%. We observed significant results, i.e., p < 0.001 for improved (AUC)0-24 and Cmax delivered via i.v. and i.n. dose. We also observed the highly significantly observations of SC CS NPs (i.n.) based on their treatment results for the biochemical, neurobehavioral, and histopathological examination in the developed ischemic MCAO brain rat model. Conclusion: The excellent significant role of mucoadhesive CS NPs of SC was proven based on the enhancement in the brain bioavailability of SC via i.n. delivery in rats and easy targeting of the brain for ischemic brain treatment followed by an improvement in neuroprotection based on a very small dose of SC.

Retraction Note to: A novel self-nanoemulsifying drug delivery system for curcumin used in the treatment of wound healing and inflammation.

[This retracts the article DOI: 10.1007/s13205-019-1885-3.].

Correction: Preparation of a novel curcumin nanoemulsion by ultrasonication and its comparative effects in wound healing and the treatment of inflammation.

[This corrects the article DOI: 10.1039/C9RA03102B.].

Preparation of a novel curcumin nanoemulsion by ultrasonication and its comparative effects in wound healing and the treatment of inflammation.

The aim of this study was to develop and evaluate a curcumin (Cur) nanoemulsion (NE) and enhance transdermal drug delivery. The comparative effects of Cur-NE were evaluated in terms of wound healing and anti-inflammatory action. Clove oil (oil), Tween-80 (surfactant), and PEG-400 (co-surfactant) were selected on the basis of their solubility and maximum nanoemulsion region. An aqueous micro-titration method with high-energy ultrasonication was used for the preparation of Cur-NE. This method was optimized to find the best NE, followed by a five-factor, three-level, central composite design. % oil, % S mix, ultrasonication time (min), ultrasonication intensity (%), and temperature (°C) were selected and optimized as independent variables. The optimized NE had parameters of 5.0% oil, 10% S mix, ultrasonication time (10 min), 40% ultrasonication intensity and 50 °C temperature, which were applied as independent and dependent variables. On the basis of experimental data of the dependent variables, we calculated a hydrodynamic diameter of 93.64 ± 6.48 nm, transmittance of 98.64 ± 0.37%, and PDI of 0.263 ± 0.021. TEM and SEM results revealed the smooth and spherical shape of the particles in the NE, with a zeta potential of -11.67 ± 0.11, refractive index of 1.71 ± 0.034, viscosity of 37 ± 7 cp, pH of 7.4 ± 0.07, and drug content of 98.11 ± 0.16% for the optimized Cur-NE. Cur-NE optimization with clove oil, Tween-80, and PEG-400 might be useful for enhancing the skin permeation of Cur. In conclusion, Cur-NE played a significant role in wound healing and exhibited anti-inflammatory effects, demonstrating its potential as a nanoformulation for safe and nontoxic transdermal delivery.

A novel self-nanoemulsifying drug delivery system for curcumin used in the treatment of wound healing and inflammation.

The main objective of this study was to develop and evaluate self-nanoemulsifying drug delivery system (SNEDDS) of curcumin (Cur) to enhance their solubility as well as improve skin permeation; and evaluate wound healing potential of Cur via SNEDDS in comparison with standards pure eucalyptus oil-SNEDDS (Euc-SNEDDS), pure curcumin suspension (Cur-S), and standard fusidic acid followed by their anti-inflammatory action. Curcumin-loaded different SNEDDS formulations were formulated through aqueous phase titration method and the zones of SNEDDS were recognized by the construction of phase diagrams. Eucalyptus oil, Tween 80 (surfactant), and Transcutol HP (co-surfactant) were selected on the basis of their solubility and highest nanoemulsion region. Characterization of thermodynamic stability for Cur-loaded SNEDDS was evaluated by its globule size, zeta potential, polydispersity index, viscosity, % transmittance, refractive index, and surface morphology. Cur-SNEDDS (Cur-SN4) was optimized and selected on the basis of their excellent physicochemical parameters for in vivo activity. The particle size (59.56 ± 0.94 nm), % transmittance (99.08 ± 0.07%), and PDI (0.207 ± 0.011 were observed for optimized Cur-SNEDDS. TEM and SEM showed their smooth and spherical shape of the morphological characterization with zeta potential (- 21.41 ± 0.89), refractive index (1.341 ± 0.06), and viscosity (11.64 ± 1.26 cp) for optimized Cur-SNEDDS. Finally, optimized Cur-SNEDDS was used to enhance skin permeation with improvement in the solubility of Cur. However, optimized Cur-SNEDDS showed significant wound healing activity as compared with pure eucalyptus oil and Cur-S on topical application. Optimized Cur-SNEDDS showed healing of wound as compared to standard fusidic acid. Optimized Cur-SNEDDS exhibited no signs of inflammatory cells on the histopathological studies of treated rats which were recommended the safety and non-toxicity of Cur-SNEDDS. Newly developed Cur-SNEDDS could be successfully used to enhance Cur-solubility and skin permeation, as well as suggested a potential role of Cur-SNEDDS for better improvement of wound healing activity followed by anti-inflammatory action of Cur via topical application.