Colloidal Vesicular System of Inositol Hexaphosphate to Counteract DMBA Induced Dysregulation of Markers Pertaining to Cellular Proliferation/Differentiation and Inflammation of Epidermal Layer in Mouse Model.

Cancer is a global health problem and chemoprevention is a promising approach for reducing cancer burden. Inositol hexaphosphate (IP6), a natural bioactive constituent of cereals, legumes, etc., has momentous potential as an antiangiogenic agent, that specifically affects malignant cells. The shortcoming is its quick absorption on oral/topical administration. Niosomes are flexible carriers for topical drug delivery. The central venture of current research was to optimize and characterize niosomal delivery system of IP6 for treatment of skin cancer. Thin film hydration method was utilized to prepare IP6 niosomes, and these were dispersed as a suspension in a suitable base. Developed formulations were analyzed for various physicochemical and pharmacological parameters such as particle size, encapsulation efficiency, morphology, drug release, texture analysis, irritability, cell line studies, Western blotting, RT-PCR, and histopathology. IP6 niosomal suspension and IP6 in acetone displayed IC50 value at the concentration of 0.96 mM (0.63 mg/mL) and 1.39 mM (0.92 mg/mL), respectively. IP6 niosomal suspension showed significantly higher (p < 0.05) activity and showed cytotoxic effect in SK-MEL-2 cancer cell line. Crucial events of cellular proliferation and differentiation, like expression of ornithine decarboxylase (ODC), proliferating cell nuclear antigen (PCNA), cycloxygenase-2 (COX-2) and Cyclin D1 were initiated from the fourth hour through application of 7,12-dimethylbenzanthracene (DMBA) on albino mice. The DMBA altered expression of aforesaid enzymes was significantly (P < 0.001) prevented by concomitant application of niosomal formulations. Results of cell line study, Western blotting, RT-PCR, and histopathology suggested that IP6 niosomal suspension could constitute a promising approach for prevention of cellular proliferation as well as DMBA induced dysregulation of cellular proliferation/differentiation and inflammation.

Development and characterization of cellulose-polymethacrylate mucoadhesive film for buccal delivery of carvedilol.

The aim of the present work was to develop and characterize mucoadhesive film of cellulose (methyl cellulose and hydroxy propyl methyl cellulose) and polymethacrylate (Eudragit RSPO) polymers for buccal delivery of carvedilol. Drug and polymers were found to be compatible as revealed by FTIR and DSC analysis. Mucoadhesive films were prepared by solvent casting technique. Swelling studies up to 4h did not show erosion of film, which was further confirmed by SEM analysis. New, simple and precise instrumental methods were established for the evaluation of mucoadhesive strength (33.8 ± 0.37-38.4 ± 0.24 g) and film strength (331.2 ± 0.73-369.0 ± 1.00 g) of developed films. Mucoadhesive film F5 showed 88 ± 1.15% in vitro drug release and 80 ± 2.30% ex vivo drug permeation through goat buccal mucosa in 12h. Drug release and permeation followed Higuchi's model and mechanism was found to be Fickian type diffusion controlled.

Synergistic effect of silymarin and standardized extract of Phyllanthus amarus against CCl4-induced hepatotoxicity in Rattus norvegicus.

In search of the effective and standardized hepatoprotective combination therapy, silymarin and standardized extract of Phyllanthus amarus has been evaluated against CCl(4)-induced hepatotoxicity in rats. Eight groups of rats were used. The animals of group A served as normal and were given only vehicle. The animals of group B served as toxin control and were administered with CCl(4) (50% solution of CCl(4) in liquid paraffin, 2 ml/kg b.w., intraperitoneally). The animals of groups C-H received silymarin (100 mg/kg b.w.), Phyllanthus amarus aqueous extract (100 mg/kg b.w.), Phyllanthus amarus ethanolic extract (100 mg/kg b.w.), silymarin (50 mg/kg b.w.)+P. amarus aq. ext. (50 mg/kg b.w.), silymarin (50 mg/kg b.w.)+P. amarus eth. ext. (50 mg/kg b.w.) and marketed formulation (M.F.) 5 ml/kg b.w. for 6 days orally as well as CCl(4) (2 ml/kg b.w.) on 4th day intraperitoneally. The test materials were found effective as hepatoprotective as evidenced by plasma and liver biochemical parameters. The combination of silymarin and Phyllanthus amarus showed synergistic effect for hepatoprotection and silymarin with ethanolic extract of P. amarus showed better activity due to the higher concentration of phyllanthin in ethanolic extract in comparison to aqueous extract of P. amarus as estimated by HPLC.