title: [Preparation and characterization of irinotecan hydrochloride loaded PEO-PPO-PEO micelles and its mechanism of decreasing drug intestinal toxicity].
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.
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
authors: Xin-Xin
authors: XX
authors: Zhang
authors: Shi-Yan
authors: SY
authors: Guo
authors: Fei-Fei
authors: FF
authors: Li
authors: Yong
authors: Y
authors: Gan
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D001646:Bile / Q000378:metabolism; D001692:Biological Transport; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000493:pharmacokinetics; D002478:Cells, Cultured; D003967:Diarrhea / Q000139:chemically induced / Q000188:drug therapy; D004285:Dogs; D004337:Drug Carriers; D007422:Intestines / Q000187:drug effects; D000077146:Irinotecan; D061985:Madin Darby Canine Kidney Cells; D008297:Male; D008823:Micelles; D009363:Neoplasm Proteins / Q000378:metabolism; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011409:Propylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C116614:ABCG2 protein, human; D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; D000972:Antineoplastic Agents, Phytogenic; D004337:Drug Carriers; D008823:Micelles; D009363:Neoplasm Proteins; C116176:PEO-PPO-PEO; D011409:Propylene Glycols; D011092:Polyethylene Glycols; D000077146:Irinotecan; D002166:Camptothecin