Synthesis and Physicochemical Characterization of Amphiphilic Triblock Copolymer Brush Containing pH-Sensitive Linkage for Oral Drug Delivery

摘要

A novel and well-defined pH-sensitive amphiphilic triblockncopolymer brush poly(lactide)-b-poly(methacrylic acid)-b-poly(poly-n(ethylene glycol) methyl ether monomethacrylate) (PLA-b-PMAA-b-nPPEGMA) and its self-assembled micelles were developed for oralnadministration of hydrophobic drugs. The copolymer and its precursorsnwere synthesized by the combination of activators regenerated by electronntransfer atom transfer radical polymerization (ARGET ATRP) and ringopeningnpolymerization (ROP) techniques. The molecular structures andncharacteristics were confirmed by GPC, 1H NMR, and FT-IR. The criticalnmicelle concentration (CMC) values of PLA-b-PMAA-b-PPEGMA innaqueous medium varied from 1.4 to 2.6 mg/L, and the partitionnequilibrium constant (Kv) of pyrene in micellar solutions ranged fromn2.873 × 105 to 3.312 × 105. The average sizes of the self-assembled blanknand drug-loaded micelles were 140−250 nm determined by DLS in aqueous solution. The morphology of the micelles was foundnto be spherical by SEM. Nifedipine (NFD), a poorly water-soluble drug, was selected as the model drug and wrapped into thencore of micelles via dialysis method. The in vitro release behavior of NFD from the micelles was pH-dependent. In simulatedngastric fluid (SGF, pH 1.2), the cumulative release percent of NFD was relative low, while in simulated intestinal fluid (SIF, pHn7.4), more than 96% was released within 24 h. All the results showed that the pH-sensitive PLA-b-PMAA-b-PPEGMA micellenmay be a prospective candidate as oral drug delivery carrier for hydrophobic drugs with controlled release behavior.