ABSTRACT

Liver targeting of the drugs, specifıcally to the Kuppfer cells can be achieved after i.v. administration of drug loaded spherical particles. This mode of administration of drugs enhances its overall delivery to the liver via passive targeting. The purpose of this studv was: 1) To optimize pharmacokinetics and kupffer celi (KC) ııptake of catechin after i.v. administration of catechin-polvcaprolactone nanoparticles and microparticles 2) To optimize partide size for improvement in targeting to the KC with catechin polvcaprolactone spherical particles (CSP), M w/@/w solvent evaporation technique w as used to prepare CSP and particles w ere characterized for in vitro parameters, pharmacokinetics (PK) and KC ııptake. To optimize the partide size, a series of nano- and microparticles encapsıdating the sanıe drug anıounts were investigated for hepatoprotective activity. Ten different CSP of sizes ranging from 200 nm to 25 pm were sııccessfully prepared. PK parameters sııggested that nanoparticles offered better PK and enhanced KC uptake compared to microparticles, Nanoparticles resıdted in better hepatoprotection in CCf induced liver fıbrosis model compared to microparticles (Hepatoprotection rank: 365 nm >1.1 pm >3. 2 pm = 6.1 pm < 10.4 pm) suggesting that liver uptake, particularlv KC uptake is more with nanoparticles. Particles of sizes greater than 6 pm lead to reduction in liver uptake and increase in lımg uptake. The studv condudes that nanoparticules are better and optimizedfor catechin delivery to KC compared to microparticles.