DIACEREIN-LOADED NIOSOMES (DC-NS): A NEW TECHNIQUE TO SUSTAIN THE RELEASE OF DRUG ACTION

Objective: The study's main goal is to develop a suitable niosomes (NS) encapsulated drug for anti-inflammatory effects such as diacerein (DC) and to evaluate the system's vesicle size (VS), entrapment efficiency (EE %), physical stability and in vitro release. Methods: Tween (40 and 60), cholesterol, and stearylamine were used in a 1:1:0.1 molar ratios as non-ionic surfactants. Thin film hydration was used to create the NS. Results: The higher EE% was observed with NS (F11) prepared from tween 60, cholesterol and 2.5 min sonication. These formulations' release patterns were Higuchi diffusion and first order. For the stability study, NS formulations were stored at temperature between 2-8 °C for 60 d retains the most drugs when compared to room and high temperature conditions. Conclusion: The findings of this study have conclusively shown that after NS encapsulation of DC, drug release is prolonged at a constant and controlled rate

Formulation and Characterization of Metformin-Loaded Ethosomes for Topical Application to Experimentally Induced Skin Cancer in Mice

To achieve the best treatment of skin cancer, drug penetration inside the deepest layers of the skin is an important scientific interest. We designed an ethosome formulation that serves as a carrier for metformin and measured the in vitro skin permeation. We also aimed to measure the antitumor activity of the optimal ethosomal preparation when applied topically to chemically induced skin cancer in mice. We utilized a statistical Box–Behnken experimental design and applied three variables at three levels: lecithin concentration, cholesterol concentration and a mixture of ethanol and isopropyl alcohol concentrations. All formulations were prepared to calculate the entrapment efficiency %, zeta potential, size of the vesicles and drug release % after 1, 2, 4, 8 and 24 h. The size of the vesicles for the formulations was between 124 ± 14.2 nm and 560 ± 127 nm, while the entrapment efficiency was between 97.8 ± 0.23% and 99.4 ± 0.24%, and the drug release % after 8 h was between 38 ± 0.82% and 66 ± 0.52%. All formulations were introduced into the Box–Behnken software, which selected three formulations; then, one was assigned as an optimal formula. The in vivo antitumor activity of metformin-loaded ethosomal gel on skin cancer was greater than the antitumor activity of the gel preparation containing free metformin. Lower lecithin, high ethanol and isopropyl alcohol and moderate cholesterol contents improved the permeation rate. Overall, we can conclude that metformin-loaded ethosomes are a promising remedy for treating skin cancers, and more studies are warranted to approve this activity in other animal models of skin cancers

Tailoring Apixaban in Nanostructured Lipid Carrier Enhancing Its Oral Bioavailability and Anticoagulant Activity

Apixaban (Apx), an oral anticoagulant drug, is a direct factor Xa inhibitor for the prophylaxis against venous thromboembolism. Apx has limited oral bioavailability and poor water solubility. The goal of this study was to improve the formulation of an Apx-loaded nanostructured lipid carrier (NLC) to increase its bioavailability and effectiveness. As solid lipid, liquid lipid, hydrophilic, and lipophilic stabilizers, stearic acid, oleic acid, Tween 80, and lecithin were used, respectively. Utilizing Box–Behnken design, the effects of three factors on NLC particle size (Y1), zeta potential (Y2), and entrapment efficiency percent (Y3) were examined and optimized. The optimized formula was prepared, characterized, morphologically studied, and pharmacokinetically and pharmacodynamically assessed. The observed responses of the optimized Apx formula were 315.2 nm, −43.4 mV, and 89.84% for Y1, Y2, and Y3, respectively. Electron microscopy revealed the homogenous spherical shape of the NLC particles. The in vivo pharmacokinetic study conducted in male Wistar rats displayed an increase in AUC and Cmax by 8 and 2.67 folds, respectively, compared to oral Apx suspension. Moreover, the half-life was increased by 1.94 folds, and clearance was diminished by about 8 folds, which makes the NLC formula a promising sustained release system. Interestingly, the pharmacodynamic results displayed the superior effect of the optimized formula over the drug suspension with prolongation in the cuticle bleeding time. Moreover, both prothrombin time and activated partial thromboplastin time are significantly increased. So, incorporating Apx in an NLC formula significantly enhanced its oral bioavailability and pharmacodynamic activity

Molecular Network Guided Cataloging of the Secondary Metabolome of Selected Egyptian Red Sea Soft Corals

Soft corals are recognized as an abundant source of diverse secondary metabolites with unique chemical features and physiologic capabilities. However, the discovery of these metabolites is usually hindered by the traditional protocol which requires a large quantity of living tissue for isolation and spectroscopic investigations. In order to overcome this problem, untargeted metabolomics protocols have been developed. The latter have been applied here to study the chemodiversity of common Egyptian soft coral species, using only minute amounts of coral biomass. Spectral similarity networks, based on high-resolution tandem mass spectrometry data, were employed to explore and highlight the metabolic biodiversity of nine Egyptian soft coral species. Species-specific metabolites were highlighted for future prioritization of soft coral species for MS-guided chemical investigation. Overall, 79 metabolites were tentatively assigned, encompassing diterpenes, sesquiterpenes, and sterols. Simultaneously, the methodology assisted in shedding light on newly-overlooked chemical diversity with potential undescribed scaffolds. For instance, glycosylated fatty acids, nitrogenated aromatic compounds, and polyketides were proposed in Sinularia leptoclados, while alkaloidal terpenes and N-acyl amino acids were proposed in both Sarcophyton roseum and Sarcophyton acutum

Design and Optimization of Omeprazole-Curcumin-Loaded Hydrogel Beads Coated with Chitosan for Treating Peptic Ulcers

This study aimed to formulate a pharmaceutical dosage form containing omeprazole (OMP) and curcumin (CURC) to treat experimental peptic ulcers. OMP and CURC were preliminarily complexed with hydroxypropyl-β-cyclodextrin for enhancing their solubilization. After that, the combined complex (CURC/OMP) was loaded to alginate beads to sustain their release and then coated with chitosan. Finally, we tested the anti-ulcerogenic impact of the best formula versus free OMP or OMP-only-loaded beads. The formulated spherical beads’ diameter ranged from a minimum value of 1.5 ± 0.08 mm to 2.6 ± 0.24 mm; the swelling results ranged from 400.00 ± 8.5% to 800.00 ± 6.2%. The entrapment efficiency was in a range from 60.85 ± 1.01% to 87.44 ± 1.88%. The optimized formula (F8) showed a maximum EE% (87.44 ± 1.88%), swelling (800.00 ± 6.2%), and diameter in the range of 2.60 ± 0.24, with a desirability of 0.941. In the first hour following the administration of the free drug complex, 95% of OMP and 98% of CURC were released. This is unacceptable for medications that require a delayed release in the stomach. The initial drug release from hydrogel beads was 23.19% for CURC and 17.19% for OMP after 2 h and 73.09% for CURC and 58.26% for OMP after 12 h; however, after 24 h, 87.81% of CURC and 81.67% of OMP had been released. The OMP/CURC beads showed a more stable particle size (0.52 ± 0.01 mm) after 6 weeks. In conclusion, the OMP/CURC hydrogel beads give stronger anti-ulcer effectiveness compared to free OMP, CURC-only beads, and OMP-only-loaded beads, indicating a prospective application for managing peptic ulcers