Enhancement of Hepatoprotective Efficacy of Propolis by Fabrication of Liposomes, as a Platform Nano-Formulation for Multi-Component Natural Medicine

Rohan      V. Ambardekar; Kakasaheb      R. Mahadik; Anant      R. Paradkar; Abhay      M. Harsulkar

doi:10.2174/156720112802650653

Abstract

Lack of suitable formulations often obscures the potential of natural medicine. Moreover, the presence of myriad of constituents with varied physicochemical properties makes fabrication of stable phyto-formulation extremely difficult. Bee propolis is one such material that suffers inadequate clinical application, despite having diverse pharmacological activities, solely attributed to deficit of appropriate formulations. In this study, we have presented a possibility of fabricating liposomes as a platform nano-formulation for enhancement of hepatoprotective activity of propolis. Hepatoprotective efficacy of the propolis is limited by its poor oral absorption. Moreover, the exact composition of the propolis being yet undefined, indeed unconfined, it cannot be administered parenterally. In order to address the foregoing issue, propolis liposomes suitable for oral administration and having higher entrapment efficiency were formulated through a modified ethanol injection method. Effect of phospholipids (PL) and cholesterol (CH) concentration on the formulation characteristics was checked statistically by 32 factorial approach. Liposomes were characterized for vesicle diameter (Dv), entrapment efficiency (EE), zeta potential (ζ p), TEM and drug release kinetics. Clinical efficacy of the formulation was assessed using acetaminophen induced hepatotoxicity in rat model. Biochemical parameters such as AST, ALT, ALP and TBARS, as well as histopathological aspects were studied. Stable unilamellar vesicles were formed according to 32 factorial approach. Dv, EE and ζ p were ranging between 216 to 437 nm, 79.53 to 93.01% & -27.8 to -31.2 mV, respectively. Marked positive effect of PL and CH and propolis concentrations was seen on Dv as well as EE. Release of propolis in acidic media followed zero order kinetics while in alkaline media it followed 1st order kinetics. Formulation was able to suppress AST, ALT, ALP & TBARS levels in hepatotoxicity induced experimental animals and promote tissue healing, in a manner more effective than plain EEP as well as silymarin. In conclusion, suitability of liposomes as a fundamental formulation for enhancing hepatoprotective activity of multi-component propolis was justified.

Keywords: Propolis, Multi-component natural medicine, Liposomes, Factorial design, Modified Ethanol Injection, Hepatoprotective, lipophilic nature, pH-controlled pseudolatex.