Side-chain alanine-based block copolymer as natural product delivery system

Abstract

To prepare alanine containing amphiphilic block copolymers, herein, we have polymerized methyl methacrylate (MMA) by reversible addition-fragmentation chain transfer (RAFT) polymerization and further used it as macro chain transfer agent (macroCTA) for the synthesis of PMMA-b-P(Boc-L-Ala-HEMA) (Boc-L-Ala-HEMA = tert-butyloxycarbonyl-L-alanine methacryloyloxyethyl ester) diblock copolymers. The molar masses of the macroCTA and all block copolymers as well as the dispersity (Ð) of those polymers were measured by size exclusion chromatography (SEC). The Boc-group deprotection from the block copolymers was carried out in dichloromethane by using trifluoroacetic acid to produce amphiphilic PMMA-b-P(L-Ala-HEMA), and this successful deprotection was proved by 1H NMR spectroscopy. The micellar self-assembled nature of PMMA-b-P(L-Ala-HEMA) was confirmed using a variety of techniques, including dynamic light scattering (DLS), critical aggregation concentration (CAC) determination by fluorescence spectroscopy, scanning electron microscopy (SEM), atomic force microscopy (AFM), and 1H NMR spectroscopy. The hydrophobic pyrene-tagged estrone-based natural product (NP) was encapsulated in the micellar nanostructure, proven by fluorescence spectroscopy. This encapsulating power of the corresponding polymers makes them attractive candidates as drug delivery vehicles of natural products, as well as encapsulation and delivery of other hydrophobic drug/dye molecules.