title: Synthesis and physicochemical characterization of amphiphilic triblock copolymer brush containing pH-sensitive linkage for oral drug delivery.
abstract: A novel and well-defined pH-sensitive amphiphilic triblock copolymer brush poly(lactide)-b-poly(methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate) (PLA-b-PMAA-b-PPEGMA) and its self-assembled micelles were developed for oral administration of hydrophobic drugs. The copolymer and its precursors were synthesized by the combination of activators regenerated by electron transfer atom transfer radical polymerization (ARGET ATRP) and ring-opening polymerization (ROP) techniques. The molecular structures and characteristics were confirmed by GPC, (1)H NMR, and FT-IR. The critical micelle concentration (CMC) values of PLA-b-PMAA-b-PPEGMA in aqueous medium varied from 1.4 to 2.6 mg/L, and the partition equilibrium constant (K(v)) of pyrene in micellar solutions ranged from 2.873 × 10(5) to 3.312 × 10(5). The average sizes of the self-assembled blank and drug-loaded micelles were 140-250 nm determined by DLS in aqueous solution. The morphology of the micelles was found to be spherical by SEM. Nifedipine (NFD), a poorly water-soluble drug, was selected as the model drug and wrapped into the core of micelles via dialysis method. The in vitro release behavior of NFD from the micelles was pH-dependent. In simulated gastric fluid (SGF, pH 1.2), the cumulative release percent of NFD was relative low, while in simulated intestinal fluid (SIF, pH 7.4), more than 96% was released within 24 h. All the results showed that the pH-sensitive PLA-b-PMAA-b-PPEGMA micelle may be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior.
authors.affiliation: School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, P R China.
authors.forename: You Qiang
authors.initials: YQ
authors.lastname: Yang
authors.forename: Wen Jing
authors.initials: WJ
authors.lastname: Lin
authors.forename: Bin
authors.initials: B
authors.lastname: Zhao
authors.forename: Xiu Fang
authors.initials: XF
authors.lastname: Wen
authors.forename: Xin Dong
authors.initials: XD
authors.lastname: Guo
authors.forename: Li Juan
authors.initials: LJ
authors.lastname: Zhang
mesh_terms: D000284:Administration, Oral; D002627:Chemistry, Physical; D016503:Drug Delivery Systems; D006863:Hydrogen-Ion Concentration; D008689:Methacrylates / Q000138:chemical synthesis* / Q000737:chemistry*; D015394:Molecular Structure; D010316:Particle Size; D011092:Polyethylene Glycols / Q000138:chemical synthesis* / Q000737:chemistry*; D013499:Surface Properties; D013501:Surface-Active Agents / Q000138:chemical synthesis* / Q000737:chemistry*
chemical_list: D008689:Methacrylates; D013501:Surface-Active Agents; C574953:poly(lactide)-b-poly(methacrylic acid)-b-poly(poly(ethylene glycol) methyl ether monomethacrylate); D011092:Polyethylene Glycols