Alendronate-Conjugated Amphiphilic Hyperbranched Polymer Based on Boltorn H40 and Poly(ethylene glycol) for Bone-Targeted Drug Delivery

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• 作者：Hongying Chen ; Guolin Li ; Huirong Chi ; Dali Wang ; Chunlai Tu ; Lijie Pan ; Lijuan Zhu ; Feng Qiu ; Fulin Guo ; Xinyuan Zhu
• 刊名：Bioconjugate Chemistry
• 出版年：2012
• 出版时间：September 19, 2012
• 年：2012
• 卷：23
• 期：9
• 页码：1915-1924
• 全文大小：550K
• 年卷期：v.23,no.9(September 19, 2012)
• ISSN：1520-4812

文摘

A novel type of alendronate(ALE)-conjugated amphiphilic hyperbranched copolymer based on a hydrophobic hyperbranched Boltorn H40 (H40) core with ALE targeting moiety and many hydrophilic poly(ethylene glycol) (PEG) arms was synthesized as a carrier for bone-targeted drug delivery. The star copolymer H40-star-PEG/ALE was characterized using nuclear magnetic resonance (NMR), Fourier transformed infrared spectroscopy (FTIR), and gel permeation chromatography (GPC) analysis. Benefiting from its highly branched structure, H40-star-PEG/ALE could form micelles in aqueous solution, which was confirmed by transmission electron microscopy (TEM) and dynamic light scattering (DLS) techniques. The cytotoxicity and hemolysis of the H40-star-PEG/ALE micelles were evaluated via methylthiazoletetrazolium (MTT) assay against NIH/3T3 normal cells and red blood cell (RBC) lysis assay, respectively. As a model anticancer drug, doxorubicin (DOX) was encapsulated into the H40-star-PEG/ALE micelles. The anticancer activity of DOX-loaded micelles was evaluated by MTT assay against an HN-6 human head and neck carcinoma cell line. The strong affinity of H40-star-PEG/ALE micelles to bone was confirmed by the hydroxyapatite (HA) binding assay. These results indicate that the H40-star-PEG/ALE micelles are highly promising bone-targeted drug carriers for skeletal metastases.