Effect of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2)
文献类型：期刊论文
| 作者 | Guo, Shiyan; Zhang, Xinxin ; Gan, Li; Zhu, Chunliu; Gan, Yong
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| 刊名 | JOURNAL OF PHARMACY AND PHARMACOLOGY
 |
| 出版日期 | 2010-08 |
| 卷号 | 62期号:8页码:973-984 |
| 关键词 | biliary excretion breast cancer resistance protein (BCRP) intestinal toxicity irinotecan hydrochloride (CPT-11) poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles |
| ISSN号 | 0022-3573 |
| DOI | 10.1111/j.2042-7158.2010.01128.x |
| 文献子类 | Article |
| 英文摘要 | Objectives Intestinal toxicity and low levels of systemic drug exposure are among the major problems associated with tumour therapy. We have developed poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) (PEO-PPO-PEO) micelles loaded with irinotecan hydrochloride (CPT-11) hoping to decrease CPT-11-induced intestinal toxicity while increasing its systemic exposure. In addition, we have investigated the potential involvement of breast cancer resistance protein (BCRP) in biliary excretion, pharmacokinetics, and intestinal toxicity of CPT-11. Methods PEO-PPO-PEO micelles were prepared using PEO20-PPO70-PEO20 and lecithin. The effect of PEO-PPO-PEO micelles on BCRP-mediated cellular accumulation and transport efflux of CPT-11 was evaluated in MDCKII/BCRP cells. The biliary excretion, intestinal damage, and pharmacokinetic study of CPT-11-loaded PEO-PPO-PEO micelles were investigated in rats. Key findings The obtained micelles could effectively inhibit BCRP-mediated CPT-11 efflux in MDCKII/BCRP cells, and significantly decrease the drug biliary excretion in rats. Moreover, intestinal toxicity, assessed by microscopic examination of pathological damage, was ameliorated in rats injected with PEO-PPO-PEO micelles compared with rats injected with CPT-11 alone. Treatment with PEO-PPO-PEO micelles resulted in prolonged circulation time in blood and increased bioavailability of CPT-11 and SN-38 (7-ethyl-10-hydroxycamptothecin). Conclusions PEO-PPO-PEO micelles were identified as promising carriers able to reduce intestinal toxicity and increase antitumour therapeutic effect of CPT-11. The study indicated a potential involvement of BCRP in CPT-11 pharmacokinetics and CPT-11-induced intestinal toxicity. |
| WOS关键词 | PHARMACEUTICAL EXCIPIENTS ; METABOLITE SN-38 ; CPT-11 ; CAMPTOTHECIN ; DRUG ; DIARRHEA ; CELLS ; GLUCURONIDATION ; ABSORPTION ; SUBSTRATE |
| 资助项目 | National Natural Science Foundation of China[30901865] ; National Science & Technology Major Project 'Key New Drug Creation and Manufacturing Program'[2009ZX09301-001] ; National Basic Research Program of China[2009CB930300] |
| WOS研究方向 | Pharmacology & Pharmacy |
| 语种 | 英语 |
| WOS记录号 | WOS:000280202300003 |
| 出版者 | WILEY |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278820]  |
| 专题 | 药物制剂研究中心 |
| 通讯作者 | Gan, Yong |
| 作者单位 | Chinese Acad Sci, Shanghai Inst Mat Med, Shanghai Inst Biol Sci, Shanghai 201203, Peoples R China |
| 推荐引用方式 GB/T 7714 | Guo, Shiyan,Zhang, Xinxin,Gan, Li,et al. Effect of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2)[J]. JOURNAL OF PHARMACY AND PHARMACOLOGY,2010,62(8):973-984. |
| APA | Guo, Shiyan,Zhang, Xinxin,Gan, Li,Zhu, Chunliu,&Gan, Yong.(2010).Effect of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2).JOURNAL OF PHARMACY AND PHARMACOLOGY,62(8),973-984. |
| MLA | Guo, Shiyan,et al."Effect of poly (ethylene oxide)-poly (propylene oxide)-poly (ethylene oxide) micelles on pharmacokinetics and intestinal toxicity of irinotecan hydrochloride: potential involvement of breast cancer resistance protein (ABCG2)".JOURNAL OF PHARMACY AND PHARMACOLOGY 62.8(2010):973-984. |
入库方式： OAI收割
来源：上海药物研究所
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