Preparation and characterization of irinotecan hydrochloride loaded PEO-PPO-PEO micelles and its mechanism of decreasing drug intestinal toxicity.
- Author:
Xin-Xin ZHANG
1
;
Shi-Yan GUO
;
Fei-Fei LI
;
Yong GAN
Author Information
1. Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
- Publication Type:Journal Article
- MeSH:
ATP Binding Cassette Transporter, Sub-Family G, Member 2;
ATP-Binding Cassette Transporters;
metabolism;
Animals;
Antineoplastic Agents, Phytogenic;
administration & dosage;
adverse effects;
pharmacokinetics;
Bile;
secretion;
Biological Transport;
Camptothecin;
administration & dosage;
adverse effects;
analogs & derivatives;
pharmacokinetics;
Cells, Cultured;
Diarrhea;
chemically induced;
drug therapy;
Dogs;
Drug Carriers;
Intestines;
drug effects;
Madin Darby Canine Kidney Cells;
Male;
Micelles;
Neoplasm Proteins;
metabolism;
Polyethylene Glycols;
administration & dosage;
chemistry;
Propylene Glycols;
administration & dosage;
chemistry;
Rats;
Rats, Sprague-Dawley
- From:
Acta Pharmaceutica Sinica
2012;47(11):1534-1540
- CountryChina
- Language:Chinese
-
Abstract:
In this work, we developed PEO-PPO-PEO micelles loaded with irinotecan hydrochloride (CPT-11) using breast cancer resistance protein (BCRP) inhibitory material PEO20-PPO70-PEO20, and studied its mechanism of decreasing CPT-11 induced delayed diarrhea and intestinal toxicity. BCRP-overexpressing MDCKII (MDCKII/BCRP) cells were used to evaluate the effect of PEO20-PPO70-PEO20 and PEO-PPO-PEO micelles on transmembrane transport of CPT-11 in vitro. The biliary excretion, delayed diarrhea and intestinal damage of CPT-11 loaded PEO-PPO-PEO micelles of rats were investigated. The results showed that the obtained micelles could decrease the biliary excretion of CPT-11, ameliorate delayed diarrhea and intestinal toxicity of rats through inhibiting BCRP-mediated CPT-11 efflux. PEO-PPO-PEO micelles were promising carriers to reduce intestinal toxicity of CPTs.
