Chitosan microparticles ionically cross-linked with poly(γ-glutamic acid) as antimicrobial peptides and nitric oxide delivery systems

The emergence of antibiotic resistance influences the effective development of therapeutics. In this paper, chitosan (CS) and poly-gamma-glutamic acid (gamma-PGA) composite microparticles were prepared and characterized as carriers for antimicrobial peptides (LL-37) and nitric oxide (NO) delivery systems. Using ionic complexation between the positively charged LL-37 and the negatively charged polyelectrolyte gamma-PGA, gamma-PGA/LL-37 microparticles with negative zeta potentials were produced. Transmission and scanning electron microscopy revealed that complexation of gamma-PGA and LL-37 alone leads to nanostructures with irregular shapes; addition of a third component, CS, is required. gamma-PGA/LL-37 composite microparticles were rewrapped by CS to obtain LL-37 loaded spherical CS/gamma-PGA composite microparticles. NO was further loaded on microparticles by the reaction of NO and LL-37 loaded CS/gamma-PGA composite microparticles under high NO pressure. The results indicated that both LL-37 and NO were co-loaded successfully in microparticles, and the composite particles could sustain LL-37 and NO release at pH 7.4, in vitro. (C) 2014 Published by Elsevier B.V.