title: Synthesis of pH-responsive chitosan nanocapsules for the controlled delivery of doxorubicin.
abstract: Well-defined chitosan nanocapsules (CSNCs) with tunable sizes were synthesized through the interfacial cross-linking of N-maleoyl-functionalized chitosan (MCS) in miniemulsions, and their application in the delivery of doxorubicin (Dox) was investigated. MCS was prepared by the amidation reaction of CS with maleic anhydride in water/DMSO at 65 °C for 20 h. Subsequently, thiol-ene cross-linking was conducted in oil-in-water miniemulsions at room temperature under UV irradiation for 1 h, using MCS as both a surfactant and precursor polymer, 1,4-butanediol bis(3-mercapto-propionate) as a cross-linker, and D-α-tocopheryl poly(ethylene glycol) 1000 succinate as a cosurfactant. With the increase in cosurfactant concentration in the reaction systems, the sizes of the resulting CSNCs decreased steadily. Dox-loaded CSNCs were readily prepared by in situ encapsulation of Dox during miniemulsion cross-linking. With acid-labile β-thiopropionate cross-linkages, the Dox-loaded CSNCs demonstrated a faster release rate under acidic conditions. Relative to free Dox, Dox-loaded CSNCs exhibited enhanced cytotoxicity toward MCF-7 breast cancer cells without any noticeable cytotoxicity from empty CSNCs. The effective delivery of Dox to MCF-7 breast cancer cells via Dox-loaded CSNCs was also observed.
authors.affiliation: Department of Chemical and Biological Engineering and ‡Institute for Lasers, Photonics and Biophotonics, University at Buffalo, The State University of New York , Buffalo, New York 14260, United States.
authors.forename: Chih-Kuang
authors.initials: CK
authors.lastname: Chen
authors.forename: Qing
authors.initials: Q
authors.lastname: Wang
authors.forename: Charles H
authors.initials: CH
authors.lastname: Jones
authors.forename: Yun
authors.initials: Y
authors.lastname: Yu
authors.forename: Hanguang
authors.initials: H
authors.lastname: Zhang
authors.forename: Wing-Cheung
authors.initials: WC
authors.lastname: Law
authors.forename: Cheng Kee
authors.initials: CK
authors.lastname: Lai
authors.forename: Qinghang
authors.initials: Q
authors.lastname: Zeng
authors.forename: Paras N
authors.initials: PN
authors.lastname: Prasad
authors.forename: Blaine A
authors.initials: BA
authors.lastname: Pfeifer
authors.forename: Chong
authors.initials: C
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D048271:Chitosan / Q000138:chemical synthesis / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry*; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D016503:Drug Delivery Systems; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006863:Hydrogen-Ion Concentration; D061986:MCF-7 Cells; D008968:Molecular Conformation; D053769:Nanocapsules / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003432:Cross-Linking Reagents; D053769:Nanocapsules; D004317:Doxorubicin; D048271:Chitosan