title: Preparation and evaluation of reduction-responsive nano-micelles for miriplatin delivery.
abstract: A reduction-responsive amphiphilic core-shell micelle for miriplatin delivery was prepared and evaluated. A pyrene-terminated poly(2-(dimethylamino) ethyl acrylate) was synthesized through reversible addition-fragmentation chain transfer polymerization with 4-cyano-4-(ethylthiocarbonothioylthio) pentanoic acid as reversible addition-fragmentation chain transfer reagent and further modified by 2,2'-dithiodiethanol and 1-pyrenebutyric acid. Self-assembled blank micelles and drug-loaded micelles were obtained by dialysis method, and the particle size was proved to be about 40 nm with narrow dispersity by dynamic laser light scattering. Morphology results showed that blank micelles and drug-loaded micelles were spherical nanoparticles confirmed by transmission electron microscope, and the critical micelle concentration was as low as 6.09 µg/mL via pyrene fluorescence probe method. The reductive sensitivity of disulfide bond in BMs was further verified by changes in particle size, pyrene fluorescence intensity ratio (I338/I333), and morphology after treatment by dithiothreitol. Moreover, drug release rate in vitro of drug-loaded micelles was evaluated and the results suggested that this amphiphilic pyrene-modified poly(2-(dimethylamino) ethyl acrylate) can be used as reduction-triggered controlled release drug delivery carrier for hydrophobic drug.
authors.affiliation: Department of pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Weifang People's Hospital, Weifang 261041, China.
authors.forename: Dejian
authors.initials: D
authors.lastname: Hu
authors.affiliation: Department of pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
authors.forename: Shangcong
authors.initials: S
authors.lastname: Han
authors.affiliation: Department of pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
authors.forename: Guowen
authors.initials: G
authors.lastname: Yan
authors.affiliation: Department of pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Ma
authors.affiliation: Department of pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Wei
authors.affiliation: Department of pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
authors.forename: Miao
authors.initials: M
authors.lastname: Yu
authors.affiliation: Affiliated Hospital of Qingdao University, Qingdao 266071, China The first two authors contributed equally to this work. ldmdrug@163.com sunyongqdu@163.com.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of pharmaceutics, School of Pharmacy, Qingdao University, Qingdao 266021, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Sun
mesh_terms: D004220:Disulfides / Q000378:metabolism; D004229:Dithiothreitol / Q000378:metabolism; D004337:Drug Carriers / Q000138:chemical synthesis*; D008823:Micelles; D046529:Microscopy, Electron, Transmission; D053758:Nanoparticles; D009944:Organoplatinum Compounds / Q000493:pharmacokinetics*; D010084:Oxidation-Reduction
chemical_list: D004220:Disulfides; D004337:Drug Carriers; D008823:Micelles; D009944:Organoplatinum Compounds; C406530:miriplatin; D004229:Dithiothreitol
keywords: Reduction-responsive; drug delivery; miriplatin; nano-micelle; passive targeting