Amphiphilic polylactic acid-b-poly(N-(3-aminopropyl) methacrylamide) copolymers: Self-assembly to polymeric micelles for gene delivery

Abstract

In this study, for the first time diblock copolymers of PLA-b-PAPMA with three different sizes were synthesized in order to fabricate cationic micelles. In this copolymer, p(APMA) block with hydrophilic cationic nature could serve as a nucleic acid condensation platform as well as the shell of micellar structure in the self-assembly process. The p(APMA) block was electrostatically complexed with nucleic acid, and formed a neutral or mildly positive charge micellar surface, thus providing the nanoparticles safety and stability. On the other hand, polylactic acid as a hydrophobic polymer in diblock copolymer structure formed core of micelles which could encapsulate hydrophobic therapeutics. The synthesized copolymers, PLA74-b-PAPMA14, PLA121-b-PAPMA22, PLA121-b-PAPMA103 were evaluated in terms of self-assembly capability, size, polydispersity index, plasmid condensation, transfection efficacy and cytotoxicity against C26 cells. Obtained results demonstrated low CMC values for all copolymers. PLA121-b-PAPMA103 diblock copolymer condensed green fluorescent protein plasmid at C/P 1 and higher, while other diblock copolymers were able to condense plasmid above C/P 70. The self-assembly structures of cationic micelles before and after plasmid condensation showed spherical morphology in SEM analysis while DLS data illustrated appropriate size (161.7 ± 8) and PDI (0.276) for PLA121-b-PAPMA103 diblock copolymer. It could be concluded that the cationic micelles with approximately the molecular weight ratio of hydrophilic block to total polymer mass of 60 % and larger than 50 % provided higher stability, condensation ability and transfection efficiency which could be attributed to the better self-assembly process and better amine groups exposure on the micellar surface.