title: Nano-scaled pH-responsive polymeric vesicles for intracellular release of doxorubicin.
abstract: Polymeric vesicles produced by spontaneous self-association of poly(acrylic acid-co-distearin acrylate) (poly(AAc-co-DSA)) with varying ratios of AAc and DSA units in aqueous solution of pH 5.0 exhibit the pH-regulated drug release behavior. Through the electrostatic interaction with ionized AAc residues, doxorubicin (DOX) molecules can be highly accommodated onto either the inner or outer surfaces of vesicles when the pH is adjusted from 5.0 to 7.4. The extent of DOX encapsulation is dependent largely on the structural transition of vesicles in response to the pH change. While the pH-evolved drug release profile varies to some extent with the distribution of DOX molecules within vesicles, the drug release from vesicles is accelerated significantly via the disruption of the electrostatic interaction of DOX species with ionized AAc moieties at pH 5.0. The DOX-loaded polymeric vesicles show promoted cellular uptake and cytotoxicity comparable to free DOX for HeLa cells. This indicates that they are probably taken up by the cells via the lipid raft-mediated endocytosis.
authors: Department of Chemical Engineering, National Chung Hsing University, Taichung, Taiwan. hscchiu@mx.nthu.edu.tw
authors: Wen-Chia
authors: WC
authors: Huang
authors: Wen-Hsuan
authors: WH
authors: Chiang
authors: Yi-Fong
authors: YF
authors: Huang
authors: Sung-Chyr
authors: SC
authors: Lin
authors: Zong-Fu
authors: ZF
authors: Shih
authors: Chorng-Shyan
authors: CS
authors: Chern
authors: Chi-Shiun
authors: CS
authors: Chiang
authors: Hsin-Cheng
authors: HC
authors: Chiu
mesh_terms: D000179:Acrylates / Q000737:chemistry; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D003692:Delayed-Action Preparations; D004075:Diglycerides / Q000737:chemistry; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D004705:Endocytosis; D006367:HeLa Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D021962:Membrane Microdomains / Q000378:metabolism; D053758:Nanoparticles; D055672:Static Electricity
chemical_list: D000179:Acrylates; D000903:Antibiotics, Antineoplastic; D003692:Delayed-Action Preparations; D004075:Diglycerides; D004317:Doxorubicin; C058146:1,2-distearin