title: Hyperbranched polyphosphates for drug delivery application: design, synthesis, and in vitro evaluation.
abstract: A water-soluble hyperbranched polyphosphate (HPHEEP) was synthesized through the self-condensation ring-opening polymerization (SCROP) of 2-(2-hydroxyethoxy)ethoxy-2-oxo-1,3,2-dioxaphospholane (HEEP), and its suitability as a drug carrier was then evaluated in vitro. Methyl tetrazolium (MTT) and live/dead staining assays indicated that HPHEEP had excellent biocompatibility against COS-7 cells. The good biodegradability of HPHEEP was observed by NMR analysis, and the degradation products were nontoxic to COS-7 cells. Flow cytometry and confocal laser scanning microscopy analyses suggested that HPHEEP could be easily internalized by vivid cells and preferentially accumulated in the perinuclear region. Furthermore, a hydrophobic anticancer drug, chlorambucil, was used as a model drug and covalently bound to HPHEEP. The chlorambucil dose of the conjugate and free drug required for 50% cellular growth inhibition were 75 and 50 microg/mL, respectively, according to MTT assay against an MCF-7 breast cancer cell line in vitro. This high activity of the conjugate may be attributed to the biodegradability of HPHEEP so as to release the chlorambucil in cells. Therefore, on the basis of its biocompatibility and biodegradability, HPHEEP could provide a charming opportunity to design some excellent drug delivery systems for therapeutic applications.
authors.affiliation: School of Chemistry and Chemical Engineering, State Key Laboratory of Metal Matrix Composites, Shanghai Jiao Tong University, 800 Dongchuan Road, Shanghai, 200240, PR China.
authors.forename: Jinyao
authors.initials: J
authors.lastname: Liu
authors.forename: Wei
authors.initials: W
authors.lastname: Huang
authors.forename: Yan
authors.initials: Y
authors.lastname: Pang
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhu
authors.forename: Yongfeng
authors.initials: Y
authors.lastname: Zhou
authors.forename: Deyue
authors.initials: D
authors.lastname: Yan
mesh_terms: D000818:Animals; D018906:Antineoplastic Agents, Alkylating / Q000008:administration & dosage; D001672:Biocompatible Materials / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D019556:COS Cells; D018929:Cell Culture Techniques; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002699:Chlorambucil / Q000008:administration & dosage; D002522:Chlorocebus aethiops; D004337:Drug Carriers / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D016503:Drug Delivery Systems; D015195:Drug Design; D005434:Flow Cytometry; D009682:Magnetic Resonance Spectroscopy; D018613:Microscopy, Confocal; D015394:Molecular Structure; D011122:Polyphosphates / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D012995:Solubility
chemical_list: D018906:Antineoplastic Agents, Alkylating; D001672:Biocompatible Materials; D004337:Drug Carriers; D011122:Polyphosphates; D002699:Chlorambucil