Preparation, characterization and In Vivo evaluation of dexamethasone nanoparticles for the treatment of liver fibrosis

Background: The purpose of this study was to formulate nanoparticles containing Dexamethasone and to investigate their potential in the prevention of carbon tetrachloride induced liver toxicity. Methods: Dexamethasone nanoparticles were formulated using o/w emulsion solvent evaporation technique using poly-e-caprolactone as polymer. Four different nanoparticle formulations (DXMNP1, DXMNP2, DXMNP3 and DXMNP4) were prepared by taking different drug to polymer ratios. The prepared particles were characterized for particle size, drug content, PDI, surface charge potential and in-vitro drug release. The pharmacokinetics and pharmacodynamics of the Dexamethasone formulations were evaluated in male Wistar rats following iv administration, using Dexamethasone solution as reference. The pharmacokinetic parameters in rats were calculated and compared by statistical analysis. Serum glutamic pyruvic transaminase (SGPT) and Serum glutamic oxaloacetic transaminase (SGOT) were elevated. Results: The DXM nanoparticles were successfully prepared using double emulsion solvent evaporation technique. The nanoparticle formulations effectively sustained the release of the drug for more than 10 days both in vitro and in vivo. They also offered better pharmacokinetic properties to the drug than that afforded by the free drug itself. Intravenous nanoparticular administration reversed serum liver enzyme levels by 92%, compared to 60% for repeated iv administration of the solution form. Conclusion: DXM Nanoparticles showed better pharmacokinetic properties and had better prevention of liver toxicity when compared with solution.