Synthesis of RAFT-Mediated Amphiphilic Graft Copolymeric Micelle Using Dextran and Poly (Oleic Acid) toward Oral Delivery of Nifedipine

A novel, pH-responsive supramolecular graft copolymeric micelle, composed of dextran and poly (oleic acid), has been synthesized through reversible addition fragmentation chain transfer polymerization with controlled M-n and narrow polydispersity. The structural properties of the copolymer have been studied using FTIR and H-1 NMR spectral analyses. Critical micelle concentration (CMC) has been determined fluorometrically and conductometrically. The copolymer shows pH responsive micellar stability, which has been confirmed using DLS study. Dextran-g-OA copolymer demonstrates spherical morphology at CMC, while rod-like assembly has been evidenced beyond CMC that is probably because of the structural alteration of copolymeric chains at higher copolymer concentration. Dextran-g-OA is noncytotoxic toward MG-63 cells. As the self-assemble nature of copolymer micelle promotes the oral administration of hydrophobic drugs, nifedipine (NFD, a hydrophobic drug) has been used as model drug that has been encapsulated substantially into the core of the micelle. The copolymer releases the loaded NFD at a much slower rate in simulated gastric fluid (pH 1.2) and relatively faster in simulated intestinal fluid (pH 7.4) with a cumulative release of similar to 95% within 24 h, suggesting an ideal candidate as nifedipine carrier. (c) 2018 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2354-2363