Indomethacin-loaded methoxy poly(ethylene glycol)/ poly(epsilon-caprolactone) diblock copolymeric nanosphere: pharmacokinetic characteristics of indomethacin in the normal Sprague-Dawley rats.

摘要

We prepared the drug-loaded polymeric nanospheres composed of the methoxy poly(ethylene glycol) (MePEG) and poly(epsilon-caprolactone) (PCL) that showed a narrow size distribution and average diameter of less than 200 nm. We could obtain the nanosphere having a relatively high drug-loading efficiency of about 42% when the feed weight ratio of indomethacin (IMC) to polymer was 1:1. To investigate the IMC pharmacokinetics in the IMC-loaded MePEG/PCL nanosphere (DMEP70) using the rats as animal model, we analyzed the IMC concentration in plasma with HPLC after i.v. bolus administered at a dose of 10 mg/kg in free IMC (control) and IMC-loaded MePEG/PCL nanosphere (DMEP70) groups via tail vein. Pharmacokinetics parameters (mean +/- s.d.) such as the mean residence time (MRT, h), the steady-state volume of distribution (Vdss, l), the terminal half-time (t 1/2, h) and the plasma clearance (CL, l/h) of IMC in each groups (control vs. DMEP70) were determined; MRT (16.97 +/- 4.83 vs. 28.69 +/- 11.28, p < 0.01); Vdss (14.26 +/- 4.86 vs. 20.37 +/- 12.04, p < 0.05); t 1/2 (15.12 +/- 4.77 vs. 23.1 +/- 8.24, p < 0.01); CL (0.84 +/- 0.27 vs. 0.71 +/- 0.41). From these results, we could concluded that MEP70 has a significant potential for sustained release and the enhancement of circulation time of loaded drug by prolonging terminal half-life, increasing MRT and Vdss of IMC. Therefore, The MePEG/PCL block copolymeric nanosphere system is being considered as promising biodegradable and biocompatible drug carrier vehicles for parentral use and may be useful as sustained release injectable delivery systems for hydrophobic drugs.