β-Cyclodextrin-Centered Star-Shaped Amphiphilic Polymers for Doxorubicin Delivery

• DOI: 10.2217/nnm.09.108
• Publication Date: 2010-02-11T13:44:06Z
• Authors: Li Yan Qiu; Rong Juan Wang; Cheng Zheng; Yi Jin; Le Qun Jin
• Keywords: Cytoplasm; Magnetic Resonance Spectroscopy; Microscopy, Confocal; Polymers; Rhodamines; beta-Cyclodextrins; 02 engineering and technology; Cell Line; 3. Good health; Drug Delivery Systems; Spectrometry, Fluorescence; Microscopy, Electron, Transmission; Models, Chemical; Doxorubicin; Cell Line, Tumor; Humans; 0210 nano-technology; Micelles

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.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.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.