PARENTERAL ADMINISTERED SUSTAINED RELEASE PIPERINE MICROPARTICLES INTENDED FOR TREATMENT OF LIVER FIBROSIS

The objective of this work was to formulate and characterize microparticles containing piperine, and evaluate their activity against carbon tetrachloride (CCl₄)-induced liver toxicity. Piperine microparticles were formulated by o/w emulsion solvent evaporation technique using poly-ε-caprolactone as a polymer. Four different microparticle formulations (PM1, PM2, PM3, and PM4) were prepared by varying the drug/polymer ratio. The particles were characterized for particle size, drug content, surface morphology, and in-vitro drug release. The pharmacokinetics and pharmacodynamics of the piperine formulations in male Wistar rats were evaluated following intraperitoneal administration, using piperine solution as reference. The hepatoprotective activity of the formulation was determined in a CCl₄-treated rat model and also compared with piperine solution. Piperine microparticles were successfully prepared using o/w emulsion solvent evaporation technique. The microparticles sustained the release of the drug both in-vitro and in-vivo for up to 10 days and offered better pharmacokinetic properties than the free drug itself. Microparticle formulation tested in-vivo demonstrated better pharmacokinetics and pharmacodynamics compared to the reference. Drug levels in the liver were significantly higher with the microparticular formulation. The piperine microparticles produced a significant decrease in both transaminase levels when challenged with CCl₄ intraperitoneally. Positive results of these studies gave an insight that microparticles are more effective and suitable for targeted and sustained drug delivery to the liver.