Indomethacin-loaded methoxy poly(ethylene glycol)/poly(D,L-lactide) amphiphilic diblock copolymeric nanospheres: Pharmacokinetic and toxicity studies in rodents
✍ Scribed by So Yeon Kim; Young Moo Lee; Ju Seop Kang
- Publisher
- John Wiley and Sons
- Year
- 2005
- Tongue
- English
- Weight
- 446 KB
- Volume
- 74A
- Category
- Article
- ISSN
- 1549-3296
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✦ Synopsis
Abstract
Biodegradable methoxy poly(ethylene glycol)/poly(D,L‐lactide) amphiphilic block copolymeric nanospheres were prepared for application as a particulate drug carrier. Drug‐loaded nanospheres (ML50) showed a narrow size distribution with the average diameter of <200 nm. When the feed weight ratio of indomethacin (IMC) to polymer was 1:1, the ML50 nanosphere having a relatively high drug‐loading efficiency of about 33.0% could be obtained. To investigate pharmacokinetic characteristics of IMC in rats, the IMC concentration in plasma was analyzed using a high‐performance liquid chromatography system after intravenous bolus injection of free IMC and IMC‐loaded ML50 nanospheres. ML50 nanosphere system exhibited a significant potential for sustained release of drug and showed slow clearance of IMC, but there was no significant effect on metabolism of IMC in the rats. Median lethal dose (LD~50~) and major organs (e.g., heart, lung, liver, and kidney) toxicities were determined using ICR mice to estimate the acute toxicity of ML50 nanospheres. The LD~50~ of ML50 nanospheres determined by Litchfield‐Wilcoxon method was about 1.54 g/kg. After the mice were intraperitoneally administered with a half dose of LD~50~ for 7 days, no significant histopathologic changes were observed in ML50‐treated mice compared with normal mice in the light and electron microscopic observations of major organs. This indicates that ML50 nanospheres might be a useful candidate as a novel sustained drug carrier for hydrophobic drugs. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res, 2005