(418cd) Facile Access to Cation Functional Biodegradable Microparticles

Biodegradable polylactide(PLA), poly(lactic-co-glycolic acid)(PLGA) and poly(ε-carpolactone)(PCL) microparticles bearing a cationic surface have been investigated for mucoadhesive sustained release of therapeutic proteins, peptides, gene and vaccines. In the past years, different approaches have been developed to achieve a positively charged surface by either adsorbing cationic agents and surfactants or coating with polyelectrolyte, which is not very stable [1]. Here, we report on facile preparation of robust cationic biodegradable microparticles by treating poly(L-lactide-co-vinyl sulfone carbonate) (P(LLA-co-VSC)) microparticles with cationic mucoadhesive agents such as cysteamine and glycol chitosan.

P(LLA-co-VSC) random copolymers were synthesized by ring-opening copolymerization of L-lactic acid and vinyl sulfone carbonate (VSC) [2]. The microspheres based on P(LLA-co-VSC) were prepared by water-in-oil-in-water (W/O/W) emulsion process, followed by Michael-type conjugate addition with the thiol group of 2-mercaptoethylamine and the amine group of glycol chitosan, respectively. The results showed the P(LLA-co-VSC)_3.57% microparticles had an  average size of  ca. 4 μm and a narrow particle size distribution. ¹HNMR and XPS results displayed successful modification of microparticles with cationic agents under mild aqueous condition. SEM showed that cationic microparticles had a smooth surface morphorgy and a slightly increased particle size. Notably, the immobilization of glycol chitosan on the microspheres resulted in an increase of zeta potential to ca. +13 mV. The fluorescence images demonstrated obvious surface conjugation of amine-containing molecules. This gentle surface functionalization is important to maintain the bioactivity of proteins/peptides, gene and vaccines.