Beta-cyclodextrin-centered star-shaped amphiphilic polymers for doxorubicin delivery.
OBJECTIVE
Delivery of doxorubicin could be achieved by a novel micellar system based on beta-cyclodextrin-centered star-shaped amphiphilic polymers (sPEL/CD). This study specifically explored the effect of polylactide segments in sPEL/CD on various micelle properties, such as the critical micelle concentration, size, drug loading, cytotoxicity and drug resistance reversing effect.


METHODS
The sPEL/CD was synthesized by the arm-first method. The critical micelle concentrations of polymeric micelles were determined by fluorescence spectrophotometry using pyrene as a probe. The oil/water method was applied to prepare doxorubicin-loaded micelles. 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide, confocal laser-scanning microscopy and flow cytometry were used to examine cell cytotoxicity and cellular uptake of the doxorubicin-loaded micelles. Finally, rhodamine-123 cellular uptake was determined to evaluate the polymer action on MCF-7 and MCF-7/ADR cells.


RESULTS
All polymers exhibited low cytotoxicity and their micelles had a desirable release-acceleration pH (pH 5.0) for cytoplasmic drug delivery. With the introduction of polylactide into the polymer, the micelle critical micelle concentration can be effectively decreased and the drug-loading content was enhanced. Most importantly, the drug resistance of MCF-7/ADR cells was significantly reversed via the interaction between polymer and Pgp. Therefore, this type of polymer has potential superiority for cancer therapy.
Institute of Pharmaceutics, College of Pharmaceutical Sciences, Zhejiang University, 388 Yu-Hang-Tang Road, Hangzhou, 310058, China. lyqiu@zju.edu.cn
Li Yan
LY
Qiu
Rong Juan
RJ
Wang
Cheng
C
Zheng
Yi
Y
Jin
Le Qun
le Q
Jin
D002460:Cell Line; D045744:Cell Line, Tumor; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000008:administration & dosage*; D016503:Drug Delivery Systems; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008823:Micelles; D018613:Microscopy, Confocal / Q000379:methods; D046529:Microscopy, Electron, Transmission / Q000379:methods; D008956:Models, Chemical; D011108:Polymers / Q000737:chemistry; D012235:Rhodamines / Q000494:pharmacology; D013050:Spectrometry, Fluorescence / Q000379:methods; D047392:beta-Cyclodextrins / Q000737:chemistry* / Q000378:metabolism
D008823:Micelles; D011108:Polymers; D012235:Rhodamines; D047392:beta-Cyclodextrins; D004317:Doxorubicin; C031215:betadex