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 CCl4
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.
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