Abstract
Therapeutic efficacy of antifibrotic drugs can be improved by targeting hepatic stellate cells (HSCs). This study investigated the prospect of developing a carrier system for the effective delivery of hesperidin by selectively targeting HSCs in fibrotic rat model. Hesperidin-loaded surface modified liposome formulations were prepared with varying quantity of lipids to optimize physicochemical characteristics. Best liposome formulation was further conjugated with a homing ligand, recognized by HSCs, to achieve a carrier system that facilitates the targeting of hesperidin. This carrier system was characterized for various physicochemical properties. The effectiveness of the bioactive carrier to prevent liver fibrosis was investigated by carrying out biochemical, biodistribution, and histopathological analyses. The pharmaceutical properties demonstrated by the ligand conjugated carrier system were optimal to facilitate selective and preferential delivery to the liver. Steady and prolonged drug release behavior with zero order kinetics displayed by prepared carrier system established its prospect to increase efficiency and decrease dosing of hesperidin. The pharmacokinetic profile of the carrier system was very distinct and exhibited rapid plasma clearance. The bio-distribution data of formulated carrier system indicates higher uptake of hesperidin predominantly by fibrotic liver with insignificant amount in non-targeted organs, which is certainly beneficial due to low risk of toxicity and lower systemic distribution. In conclusion, this developed carrier represents a potentially beneficial approach for HSCs specific targeting of hesperidin in a rat model with liver fibrosis.