Enhanced Liver Delivery and Sustained Release of Curcumin with Drug Loaded Nanoparticles after Intravenous Administration in Rats

Liver targeting drug delivery systems can improve the delivery of several drugs useful in the treatment of liver disorders such as cirrhosis and liver cancer. The objective of this study was to prepare the biodegradable nanoparticles containing curcumin, a well-known hepatoprotective agent and further to evaluate the liver targetability and sustained release of curcumin with the developed nanoformulation. Curcumin nanoparticles were prepared by double emulsion (w/o/w) solvent evaporation method using different drug polymer ratios. Poly- ε -caprolactone was used in the preparation. The prepared formulations were evaluated for particles size, surface potential, entrapment efficiency, in vitro release, drug polymer interaction. Four different formulations CNP1, CNP2, CNP3 and CNP4 were prepared. Optimized formulation (CNP3) was evaluated for pharmacokinetics and hepatoprotective activity in CCl ₄ induced liver toxicity model after i.v. administration. Optimized formulation was selected based on the size, entrapment efficiency and release characteristics. Curcumin i.v. solution and oral suspension form were used as the reference. Particle size of all formulations was in the range of 300-470 nm and the entrapment efficiencies were in the range of 75-85 %. Drug release from the nanoparticles was sustained both in vitro and in vivo. Nanoparticle formulation tested in vivo demonstrated better pharmacokinetics and pharmacodynamics compared to the reference. Drug levels in the liver were significantly higher with nanoparticular formulation. Thus, this study successfully prepared a nanoparticular formulation containing curcumin with polycaprolactone as the polymer. With the developed formulation better liver targetability was achieved.