Dalia S. Shaker

Cellular uptake, cytotoxicity and in-vivo evaluation of Tamoxifen citrate loaded niosomes

One of the main challenges in Tamoxifen cancer therapy is achieving localized, efficient and sustained delivery without harming normal healthy organs. This study focused on evaluating Tamoxifen Citrate (TMC) niosomes for localized cancer therapy through in-vitro breast cancer cytotoxicity as well as in-vivo solid anti-tumor efficacy. Different niosomal formulae were prepared by film hydration technique and characterized for entrapment efficiency% (E. E), vesicle size, morphology, and in-vitro release. The cellular uptake and anti-cancer activity were also tested in-vitro using MCF-7 breast cancer cell line. Moreover, in-vivo anti-tumor efficacy was examined in Ehrlich carcinoma mice model through reporting solid tumor volume regression and tissue TMC distribution. The obtained niosomes prepared with Span 60: cholesterol (1: 1 molar ratio) showed a distinct nano-spherical shape with EE up to 92.3%± 2.3. Remarkably prolonged release of TMC following diffusion release behavior was detected. The optimized formula showed significantly enhanced cellular uptake (2.8 fold) and exhibited significantly greater cytotoxic activity with MCF-7 breast cancer cell line. In-vivo experiment showed enhanced tumor volume reduction of niosomal TMC when compared to free TMC. Based on these results, the prepared niosomes demonstrated to be promising as a nano-size delivery vehicle for localized and sustained TMC cancer therapy.

Comparative Studies on Dissolution and Bioavailability of Tamoxifen Citrate Loaded Binary and Ternary Solid Dispersions.

Aims: This study focused on comparing binary and ternary solid dispersions (SDs) of water-insoluble Tamoxifen citrate (TMC) regarding drug dissolution and oral bioavailability. Basically, the enhanced dissolution of this drug by water-soluble polymer has not yet been reported in literature. Study Design: In vitro and In-vivo characterization of Tamoxifen citrate loaded binary and ternary solid dispersion systems. Place and Duration of Study: Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Cairo, Egypt between June 2012 and June 2013. Methodology: Amorphous SDs of TMC with two hydrophilic polymers, polyethylene glycol 6000 (PEG 6000) and Methyl cellulose (MC), were prepared by melting method. Binary SDs of TMC with PEG of different weight ratios were prepared. MC was used as third component to prepare ternary SDs. Physicochemical properties of SDs were characterized by FTIR, DSC, and In-vitro drug release in comparison with physical mixtures and the drug alone. Oral bioavailability of the optimized SD formula was compared with that of free TMC in rats. Results: Infrared spectroscopic studies suggested no interaction between TMC and Original Research Article British Journal of Pharmaceutical Research, 4(2): 215-229, 2014 216 polymers rather than H-bond formation. A remarkably improved dissolution of drug from the ternary solid dispersion systems when compared to the binary solid dispersion systems was detected. On the basis of % dissolution efficiency (% DE), the SD composed of PEG: TMC: MC in a ratio 4:1:2 w/w/w was selected as the optimized SD. The in-vivo studies showed extremely significant higher values of Cmax (P<.05), AUC0-24 (P<.05) and significantly (P<.05) lower values of Tmax exhibited by SD compared with free TMC. Conclusion: Highly enhanced TMC dissolution and bioavailability exhibited by PEG: TMC: MC ternary solid dispersion in a weight ratio 4:1:2 were promising to improve the therapeutic potential of TMC.

In Vitro and In Vivo Evaluation of Combined Time and pH- Dependent Oral Colonic Targeted Prednisolone Microspheres

Aims: to enhance the anti-inflammatory effect as well as oral absorption of prednisolone (PR), through formulation of colonic targeted microspheres prepared from a blend of time and pHdependent polymers and loaded with PR. Study Design: In Vitro and In Vivo Evaluation of Combined Time and pHDependent Oral Colonic Targeted Prednisolone Microspheres. Place and Duration of Study: Department of Pharmaceutics and Industrial Pharmacy, Helwan University, Cairo, Egypt between June 2011 and October 2012. Methodology: Microspheres were prepared by solvent evaporation method using different ethyl cellulose (EC) and Eudragit S-100 (ES100) ratios with 0.5 and 1% w/v span 80 as emulsifier. The microspheres were evaluated for surface morphology, particle size, drug encapsulation efficiency % and in vitro drug release at pH 1.2 and 7.4. The antiinflammatory activity of selected formula was compared to that of conventional PR tablets. Results: A decrease in drug entrapment efficiency % was obtained with increasing both polymers and surfactant concentrations. Based on drug release results, the formula of 1: Research Article Article British Journal of Pharmaceutical Research, 3(3): 420-434, 2013 421 1: 0.16 w/w/w, EC: ES100: PR ratio with 1% w/v span 80 was selected for further histopathological evaluation of the anti-inflammatory activity in colitis induced-rats. Histopathological study showed undefined tissue necrosis after treatment with the selected microspheres; however, diffused necrosis was observed in rats treated with the commercial tablets. In vivo absorption study showed that values of Cmax and AUC0-24 of both formulations were insignificantly different. However, the occurrence of Cmax of microspheres was significantly delayed in comparison to free drug (9.17 to 2.67hr) (P<.001). Conclusion: This study has supplied us with brightening results concerning the therapeutic efficacy of a blend of time and pHdependent polymers colonic targeted microspheres.