title: Novel Redox-Responsive Amphiphilic Copolymer Micelles for Drug Delivery: Synthesis and Characterization.
abstract: A novel redox-responsive amphiphilic polymer was synthesized with bioreductive trimethyl-locked quinone propionic acid for a potential triggered drug delivery application. The aim of this study was to synthesize and characterize the redox-responsive amphiphilic block copolymer micelles containing pendant bioreductive quinone propionic acid (QPA) switches. The redox-responsive hydrophobic block (polyQPA), synthesized from QPA-serinol and adipoyl chloride, was end-capped with methoxy poly(ethylene glycol) of molecular weight 750 (mPEG750) to achieve a redox-responsive amphiphilic block copolymer, polyQPA-mPEG750. PolyQPA-mPEG750 was able to self-assemble as micelles to show a critical micelle concentration (CMC) of 0.039% w/v (0.39 mg/ml, 0.107 mM) determined by a dye solubilization method using 1,6-diphenyl-1,3,5-hexatriene (DPH) in phosphate-buffered saline (PBS). The mean diameter of polymeric micelles was found to be 27.50 nm (PI = 0.064) by dynamic light scattering. Furthermore, redox-triggered destabilization of the polymeric micelles was confirmed by (1)H-NMR spectroscopy and particle size measurements in a simulated redox state. PolyQPA-mPEG750 underwent triggered reduction to shed pendant redox-responsive QPA groups and its polymeric micelles were swollen to be dissembled in the presence of a reducing agent, thereby enabling the release of loaded model drug, paclitaxel. The redox-responsive polyQPA-mPEG750 polymer micelles would be useful as a drug delivery system allowing triggered drug release in an altered redox state such as tumor microenvironments with an altered redox potential and/or redox enzyme upregulation.
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
authors.forename: Jungeun
authors.initials: J
authors.lastname: Bae
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
authors.forename: Abhijeet
authors.initials: A
authors.lastname: Maurya
authors.affiliation: Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.
authors.forename: Zia
authors.initials: Z
authors.lastname: Shariat-Madar
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA.|Institute for Drug Delivery and Biomedical Research (IDBR), Bangalore, India.
authors.forename: S Narasimha
authors.initials: SN
authors.lastname: Murthy
authors.affiliation: Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA. seongjo@olemiss.edu.|Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, Mississippi, 38677, USA. seongjo@olemiss.edu.
authors.forename: Seongbong
authors.initials: S
authors.lastname: Jo
mesh_terms: D016227:Benzoquinones / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008823:Micelles; D010084:Oxidation-Reduction; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D011108:Polymers / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism; D011422:Propionates / Q000008:administration & dosage / Q000138:chemical synthesis / Q000378:metabolism; D013501:Surface-Active Agents / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000378:metabolism
chemical_list: D016227:Benzoquinones; D008823:Micelles; D011108:Polymers; D011422:Propionates; D013501:Surface-Active Agents; C004532:quinone; D011092:Polyethylene Glycols; C029658:propionic acid
keywords: amphiphilic polymer; micelle; redox-responsive polymer; targeted drug delivery; trimethyl-locked quinone propionic acid