Formulation of chitosan lipid vesicle in vitro and ex vivo evaluation

Abstract

newlinev newlineABSTRACT newlineThymoquinone is one of the most widely used phytochemical which is used to treat various ailments. Despite of offering excellent therapeutic potential of phytochemicals there are various issues need to be resolved which includes high lipophilicity, low bioavailability and hostile GI environment. Therefore, the current research focused on curtailing the inherent issues of thymoquinone by formulating its nanoparticles. Thymoquinone loaded chitosan solid lipid nanoparticles were prepared by solvent evaporation method using chitosan, cholesterol, span60/tween 80 and phosphatidylcholine. Thymoquinone loaded chitosan polycaprolactone nanoparticle was also prepared by solvent evaporation method using chitosan, polycaprolactone and PVA. It was optimized using three factor three level QbD approach. The prepared nanoparticles were analysed for in-vitro, ex-vivo and in vivo evaluation. Chitosan coated solid lipid nanoparticle and chitosan polycaprolactone nanoparticle exhibited mean particle size (1.66 ± 5.83 nm and 182.32 ± 6.46 nm), polydispersity index (0.211 ± 0.016 and 0.179 ± 0.012), zeta potential (12.52 ± 1.21mV and 21.36 ± 1.22 mV), entrapment efficiency (82.66 ± 3.47% ; 79.86 ± 4.36%), drug loading (9.84 ± 0.76 % ; 13.45 ± 1.38%). Transmission electron microscopy examinations revealed spherical particle size with uniform drug distribution. In vitro drug release studies establish better release of thymoquinone from chitosan solid lipid nanoparticles and chitosan polycaprolactone nanoparticle compared to drug suspension with cumulative drug release of (71.32 ± 3.88% and 79.65 ± 4.72 %). The final optimized formulation showed enhanced permeation which was further confirmed by confocal laser scanning microscopy (CLSM). newlineFurthermore, the prepared nanoparticles represents many fold higher relative oral bioavailability compared to free thymoquinone suspension. Based on our findings, it is suggested that the prepared nanoparticles could be an excellent nanoplatform to improve the therapeutic efficac