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Loading docetaxel in β-cyclodextrin-based micelles for enhanced oral chemotherapy through inhibition of P-glycoprotein mediated efflux transport

 RSC Adv. 2017; 
Lu Zhang‡ b,  Yurun Shen‡a and Liyan Qiu
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Recombinant Proteins Chlorpromazine hydrochloride, amiloridehydrochloride and nystatin were obtained from Shanghai Chemical Reagents Co. Ltd. (Shang Hai, China). All other reagents were commercially purchasable. Madin–Darby canine kidney (MDCK) cell lines and stable MDCK-MDR1 cell lines were obtained from Genscript company (Jiangsu, China). Cells were cultured in MEM medium (10% FBS, 1% penicillin–streptomycin) and humidified atmosphere at 37 °C, 5% CO2. The mice sarcoma 180 (S180) cells were purchased from KeyGen Biotechnology Co., LTD (Nanjing, China), cultured in RPMI-1640 medium (10% FBS, 1% penicillin–streptomycin) and humidified atmosphere at 37 °C, 5% CO2. Female ICR mice (4–6 weeks old, weighing 20 ± 2 g) were purchased from Experimental Animal Center, Zhejiang Chinese Medical University (Hangzhou, China). All animal studies were conducted according to the National Institutes of Health Guide for the Care and Use of Laboratory Animals with the approval of the Scientific Investigation Board of Zhejiang University (Hangzhou, China). Get A Quote

摘要

Oral administration of BCS Class IV drugs still faces great challenges owing to their poor dissolubility in the gastro-intestinal (GI) tract and low permeation capacity across the GI membrane. Here, we constructed a β-cyclodextrin-based polymeric micelle (PELC) to effectively deliver docetaxel (DTX), a typical BCS Class IV drug, by oral administration. Cellular uptake and bidirectional transport studies of PELC/DTX on MDCK-MDR1 cells revealed significantly enhanced absorption of DTX through inhibition of P-glycoprotein mediated efflux. In vivo pharmacokinetic studies showed that the relative oral bioavailability of PELC/DTX was 4.6-fold higher than free DTX. Correspondingly, orally administered PELC/DTX achi... More

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