Novel resveratrol smart lipids; design, formulation, and biological evaluation of anticancer activity.

PURPOSE: Although resveratrol (RES) is an efficacious molecule, its therapeutic activity is impeded by significant limitations, such as rapid oral absorption, poor oral bioavailability, and low water solubility. Therefore, the preparation of RES in different pharmaceutical carriers represents an important tool to enhance its therapeutic applications. This study aims to potentiate the anti-cancer activity of RES by formulating it into a novel nanocarrier called Smart Lipid. METHODS: RES-loaded Smart Lipids were prepared by high-shear hot homogenization method utilizing a 21 × 32 factorial design with three factors at different levels: the total lipid concentration, the concentration of surfactant, and the type of surfactant. The responses were evaluated based on entrapment efficiency percentages and particle size. RESULTS: Our novel optimized RES-loaded Smart Lipid formula showed small particle size (288.63 ± 5.55 nm), good zeta potential (-16.44 ± 0.99 mV), and an entrapment efficiency of 86.346 ± 3.61% with spherical, clearly distinct, and no signs of fusion by transmission electron microscopy. Further characterization was done using differential scanning calorimetry, which showed no interaction between the drug and other components as the optimum lyophilized formula showed a peak at 54.75°C, which represents the lipid mixture, with an undetectable characteristic peak of the drug, which indicates entrapment of the drug, and the structure of the compounds was confirmed by Fourier transform-infrared spectroscopy, in which the majority of the drug's characteristic peaks disappeared when loaded into Smart Lipid, which may indicate Smart Lipid's ability to reduce the stretching and bending between bonds in RES. In addition, the optimized formula showed a sustained release pattern compared to RES suspension. Finally, the cytotoxic activity of the optimized RES-loaded Smart Lipid on different cell lines (human breast adenocarcinoma (MCF7), human hepatocellular carcinoma (HepG2), and human colon cancer cells (HT29)) was assessed through MTT assay (7-fold reduction in the IC50, from 3.7 ± 0.5 µM for free RES to 0.5 ± 0.033 µM for Smart Lipid loaded formula against MCF7, 3-fold reduction in the IC50 against HepG2 cells, from 10.01 ± 0.35 to 3.16 ± 0.21 µMm, and a more than 10-fold reduction in the IC50 from more than 100 to 10 ± 0.57 µM against HT-29 cells) and its effect on cell cycle progression and apoptosis induction were assessed using flow cytometry and annexin V kit, respectively. Our results showed that RES-loaded Smart Lipid significantly reduced cell viability, induced cell cycle arrest at G0/G1 phase, and apoptosis compared to free formula and free RES suspension. CONCLUSION: Loading RES into this novel kind of nanocarrier enhanced RES absorption, cellular accumulation, and improved its anticancer properties.

Evaluation of muco-adhesive tacrolimus patch on caspase-3 induced apoptosis in oral lichen planus: a randomized clinical trial.

BACKGROUND: The study compared the clinical effectiveness of topical Tacrolimus (TAC) in patches or gel with Triamcinolone acetonide (TRI) gel for erosive/atrophic oral lichen planus (OLP) and investigated the influence of these therapies on Caspase-3 expression as a marker of apoptosis. METHODS: Thirty patients were randomly assigned into three equal groups to receive either topical TAC 0.1% patch twice daily, topical TAC 0.1% gel, or topical TRI 0.1% gel four times daily for 8 weeks. Each patient's clinical score (CS), visual analogue scale (VAS), and total atrophic area (TAA) of the marker lesion were measured at baseline, 2, 4, and 8 weeks of treatment, as well as after 4 weeks of treatment free period. Caspase-3 expression and lymphocytic counts (LC) were assessed in pre- and post-treatment biopsied stained sections. RESULTS: TAC patch resulted in a higher reduction in CS [- 14.00 (15.54%)] and VAS [- 70.21 (15.82%)] followed by TAC gel then TRI gel within the first two weeks. The reduction in VAS and TAA were significantly higher in TAC groups compared to TRI gel, although the difference between TAC treatment was not significant and this was observed throughout the treatment and follow-up periods. Caspase-3 expression increased in connective tissue in all groups. It decreased significantly within the epithelium in both TAC groups but increased in TRI gel. (LC) were significantly lowered with the TAC patch compared to other groups. The percentage change in Caspase-3 epithelial expression was significantly correlated to the CS, TAA, and LC. CONCLUSION: Both TAC patch and gel significantly decreased pain and lesion size than TRI gel, with a significant reduction in Caspase-3 expression within the epithelium in comparison to the increase seen with TRI gel. The study protocol was registered at www. CLINICALTRIALS: gov (NCT05139667) on 01/12/2021.

Silymarin loaded floating polymer(s) microspheres: characterization, in-vitro/in-vivo evaluation.

Silymarin has a short half-life (4-6 hours) which leads to necessity of frequent administration. Besides, it suffers from intestinal degradation. Thus, our study aims to formulate encapsulated floating microspheres using different polymers as HPMC, EC and a blend of them. Emulsion solvent evaporation technique was applied for preparation of microspheres. Parameters considered during preparation are drug: polymer ratio and emulsifier concentration. Selected formulations were characterized by SEM and subjected for assessment by drug entrapment efficiency, buoyancy for 12 hr, in- vitro drug release, kinetics of release and stability. In-vivo bio-equivalence study was performed using albino rabbits. Formula F24 (treatment II) exhibited high % buoyancy (73.4), higher t90 (190.7 day), high Cmax (1021.3 ng/ml) and Tmax (6 h) with a significant difference between it and treatment I (Silymarin plus) after carrying out ANOVA study. Also formula F24 exhibited MRT (hr) equal 9.44 ± 0.03 and high relative bioavailability RB% (227%), which indicates promising microspheres that could be used for effective management of liver disease.

Formulation, development, and in-vitro/ex-vivo evaluation of vaginal bioadhesive salbutamol sulfate tablets for preterm labor.

Preterm labor is the main cause of death and serious illness of both infants and pregnant women in Africa and worldwide. Parenteral and oral salbutamol sulfate as a B2 antagonist has been used for the treatment of preterm labor. The study aims are to formulate salbutamol sulfate non-invasive vaginal bioadhesive tablets to avoid the side effects of conventional formulations. Full factorial design 41 ×31 ×21 was used for the preparation of 24 vaginal bioadhesive tablet formulations. The independent factors were polymer type (Carbopol 934, HPMC 4000, HEC, and PEG 6000), polymer to drug ratio (1:1, 2:1, and 3:1), and diluent (lactose and mannitol). Vaginal bioadhesive tablets were evaluated for residence time and time required for release 50% of salbutamol sulfate T50% as dependent variables. The formulations were evaluated in terms of drug content, mass variation, hardness, friability, swelling index, residence time, and in-vitro drug release. Results revealed that polymer and diluent types are the most significant factors in both residence time and T50%. A strong positive correlation (0.91) between in-vitro and ex-vivo permeation was observed, which predict the best in-vivo performance of salbutamol vaginal bioadhesive tablet. Thus, salbutamol sulfate vaginal bioadhesive tablets could be a successful remedy for preterm labor.

Pharmaceutical and pharmacokinetic evaluation of novel rectal mucoadhesive hydrogels containing tolmetin sodium.

The objective of the present study was to develop rectal mucoadhesive hydrogels loaded with Tolmetin Sodium, a non-steroidal anti-inflammatory drug, for prolonged duration of action and increased bioavailability. Fourteen formulae were prepared with different types and concentrations of polymers as hydroxypropylmethyl cellulose, hydroxylethyl cellulose, carboxymethyl cellulose and sodium alginate. Each formulation contain Tolmetin Sodium equivalent to 5% w/w active drug. The effect of the employed gel bases on pH, gel strength, mucoadhesion, viscosity and the in vitro release profile of drug was examined. In addition, hydrogel formulations were subjected to rheological and stability studies. The physicochemical characterization revealed that all hydrogels had a suitable pH (6.64-7.75) and gel strength (15.5-65.29 s) for rectal application. The in-vitro drug release from the formulations showed a controlled drug release pattern, reaching 72-92.6% after 8 h. The kinetic analysis of the release data revealed that the drug release from all tested hydrogel bases obeyed the diffusion mechanism. The degradation of Tolmetin Sodium from its rectal hydrogel formulations was found to be a zero-order reaction. All formulations except sodium alginate hydrogel were quite stable. Considering the in-vitro release, rheological properties and shelf life, (CMC; 2%w/w) hydrogel formula was the best among the studied formulations. Therefore, further histopathological and bioavailability studies were carried out to detect different pharmacokinetic parameters of the established formulations compared with commercially available capsules. Formula containing 2% CMC showed relative bioavailability 357.93%. Finally, good correlation was observed between in-vitro and in-vivo profile.