Amino Acid Inspired Alginate-Based pH Sensitive Polymeric Micelles via Reversible Addition–Fragmentation Chain Transfer Polymerization

Abstract

Biopolymeric micelles derived from bioinspired amphiphilic polymers are drawing noteworthy attention as carriers for hydrophobic drugs since they possess a hydrophobic core and a hydrophilic cell. Herein, a hydrophobic monomer N-Boc glycine-hydroxy methyl methacrylate (Gly-HEMA) has been synthesized by chemical modification of N-Boc glycine. This monomer has further been grafted through reversible addition–fragmentation chain transfer (RAFT) polymerization on the backbone of sodium alginate (hydrophilic) to obtain an amphiphilic copolymer with an attached hydrophobic segment. The controlled polymerization is assessed using advanced polymer chromatographic (APC) analysis with a narrow dispersity. The critical micelle concentration (CMC) of the developed copolymer [i.e., Alg-g-p(Gly-HEMA)] has been determined by surface tension measurement and photoluminescence (PL) spectroscopic and dynamic light scattering (DLS) analyses. The size and morphology of the developed micelle have been investigated by field emission scanning electron microscopy (FESEM) and high-resolution transmission electron microscopy (HRTEM) analyses, which reveal that the size of the copolymeric micelle is ∼200 nm with a spherical shape. Alg-g-p(Gly-HEMA) has demonstrated pH-responsive reversible micellization behavior. The process of micellization to phase separation and vice versa can be controlled just by altering the pH. The formed micelle is able to uptake the hydrophobic drug indomethacin (% of loading: ∼34%) and release it in a controlled manner, as apparent from an in vitro study.