PLA-b-SMA as an amphiphilic diblock copolymer for encapsulation of lipophilic cargo.

Abstract

The encapsulation of active pharmaceutical ingredients (APIs) within drug delivery systems such as polymeric nanoparticles (PNPs) vastly improves the therapeutic efficiency of the incorporated APIs. PNPs synthesized using amphiphilic block copolymers are efficient drug delivery systems as the hydrophobic block facilitates the encapsulation of lipophilic components and the hydrophilic block constitutes the hairy corona of the PNP that stabilizes the nanocarriers against aggregation in solution. Poly(styrene-alt-maleic acid) (SMA) is an attractive polymer for the hydrophilic corona of PLA-based nanoparticles as it allows for post polymerization functionalization and aids in the prevention of NP aggregation. The synthesis of a novel PLA-b-SMA block copolymer, via sequential ring opening polymerization (ROP) and reversible addition–fragmentation chain transfer (RAFT) polymerization, is presented. PLA macro-CTAs, synthesized via ROP, can be chain extended via RAFT copolymerization of styrene and maleic anhydride to yield PLA-b-SMAnh and via RAFT polymerization of N-vinylpyrrolidone to yield PLA-b-PVP block copolymers. Controlled hydrolysis of the anhydride moieties converts PLA-b-SMAnh into PLA-b-SMA. Monodisperse PLA-b-SMA and PLA-b-PVP nanoparticles (NPs) ranging in diameter between 60 and 220 nm are prepared. The lipophilic fluorescent dye DiI is encapsulated within the NPs successfully and these fluorescent NPs are used in a preliminary cell uptake study.