A de novo formulation of metformin using chitosan-based nanomicelles for potential diabetes therapy

A de novo formulation of metformin (MET) was developed through the physical loading of drug into a chitosan-grafted-[poly(acryl amide)-block-poly(acrylic acid)] [CS-g-(PAAm-b-PAA)] terpolymer. For this purpose, CS was functionazed with phthalic anhydride followed by 4-cyano, 4-[(phenylcarbothioyl)sulfanyl]pentanoic acid to produc a macro-RAFT agent (CS-CTA). Afterward, acryl amide and acrylic acid monomers were graft and block copolymerized onto the synthesized CS-CTA through a reversible addition-fragmentation chain transfer (RAFT) polymerization technique to afford CS-g-PAAm copolymer and CS-g-(PAAm-b-PAA) terpolymer, respectively. The fabricated CS-g-(PAAm-b-PAA) terpolymer was loaded with MET as an anti-diabetic drug, and its drug release behavior was evaluated in the body simulated environment. As results, it was concluded that the fabricated CS-g-(PAAm-b-PAA) nanosystem has high potential as de novo drug delivery system (DDS) for diabetes therapy, mainly due to controlled drug release profile in comparison with conventional formulations of MET. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 136, 48037.