title: Alendronate-conjugated amphiphilic hyperbranched polymer based on Boltorn H40 and poly(ethylene glycol) for bone-targeted drug delivery.
abstract: 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.
authors.affiliation: Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin 150001, People's Republic of China.
authors.forename: Hongying
authors.initials: H
authors.lastname: Chen
authors.forename: Guolin
authors.initials: G
authors.lastname: Li
authors.forename: Huirong
authors.initials: H
authors.lastname: Chi
authors.forename: Dali
authors.initials: D
authors.lastname: Wang
authors.forename: Chunlai
authors.initials: C
authors.lastname: Tu
authors.forename: Lijie
authors.initials: L
authors.lastname: Pan
authors.forename: Lijuan
authors.initials: L
authors.lastname: Zhu
authors.forename: Feng
authors.initials: F
authors.lastname: Qiu
authors.forename: Fulin
authors.initials: F
authors.lastname: Guo
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
mesh_terms: D019386:Alendronate / Q000737:chemistry* / Q000493:pharmacokinetics; D000818:Animals; D001842:Bone and Bones / Q000187:drug effects*; D045744:Cell Line, Tumor; D002850:Chromatography, Gel; D016503:Drug Delivery Systems; D005434:Flow Cytometry; D051379:Mice; D041681:NIH 3T3 Cells; D011092:Polyethylene Glycols / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared
chemical_list: D011092:Polyethylene Glycols; D019386:Alendronate