title: Block ionomer complexes of PEG-block-poly(4-vinylbenzylphosphonate) and cationic surfactants as highly stable, pH responsive drug delivery system.
abstract: A new family of block ionomer complexes (BIC) formed by poly(ethylene glycol)-block-poly(4-vinylbenzylphosphonate) (PEG-b-PVBP) and various cationic surfactants was prepared and characterized. These complexes spontaneously self-assembled in aqueous solutions into particles with average size of 40-60nm and remained soluble over the entire range of the compositions of the mixtures including stoichiometric electroneutral complexes. Solution behavior and physicochemical properties of such BIC were very sensitive to the structure of cationic surfactants. Furthermore, such complexation was used for incorporation of cationic anti-cancer drug, doxorubicin (DOX), into the core of BIC with high loading capacity and efficiency. The DOX/PEG-b-PVBP BIC also displayed high stability against dilution, changes in ionic strength. Furthermore, DOX release at the extracellular pH of DOX/PEG-b-PVBP BIC was slow. It was greatly increased at the acidic pH mimicking the endosomal/lysosomal environment. Confocal fluorescence microscopy using live MCF-7 breast cancer cells suggested that DOX/PEG-b-PVBP BICs are transported to lysosomes. Subsequently, the drugs are released and exert cytotoxic effect killing these cancer cells. These findings indicate that the obtained complexes can be attractive candidates for delivery of cationic drugs to tumors.
authors.affiliation: Department of Materials Sciences, Graduate School of Pure and Applied Sciences, University of Tsukuba, Ten-noudai 1-1-1, Tsukuba, Ibaraki 305-8573, Japan.
authors.forename: Masao
authors.initials: M
authors.lastname: Kamimura
authors.forename: Jong Oh
authors.initials: JO
authors.lastname: Kim
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Kabanov
authors.forename: Tatiana K
authors.initials: TK
authors.lastname: Bronich
authors.forename: Yukio
authors.initials: Y
authors.lastname: Nagasaki
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry; D016503:Drug Delivery Systems; D006801:Humans; D006863:Hydrogen-Ion Concentration; D063065:Organophosphonates / Q000008:administration & dosage / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry*; D011145:Polyvinyls / Q000008:administration & dosage / Q000737:chemistry*; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D063065:Organophosphonates; D011145:Polyvinyls; D013501:Surface-Active Agents; D011092:Polyethylene Glycols; C008997:polyvinylbenzyl phosphonate; D004317:Doxorubicin