Fabrication of poly(β-amino ester) and hyaluronic acid based pH responsive nanocomplex as an antibiotic release system

Abstract

World Health Organization (WHO) warns about antimicrobial resistance (AMR) considered as the most serious threats to global health, food security, and development. There are various efforts for elimination of this serious issue. These efforts include education of individuals, new policies, development of new antimicrobials and new materials for effective delivery. Novel drug delivery systems with ability of local and on-demand delivery are one of the promising approaches for prevention of AMR. In this regard, a pH-responsive antibiotic delivery system based on pH-responsive poly(beta-amino ester) (PBAE) and enzyme responsive hyaluronic acid (HA). The polymeric nanocomplexes were obtained via electrostatic complexation of PBAE and HA in the presence of a model antibiotics, colistin and vancomycin. The particle sizes at pH 7.4 were determined in the range of 131-730 nm and 120-400 nm by DLS and STEM, respectively. When pH was switched from 7.4 to 5.5, the hydrodynamic diameter increased 2.5-32 fold. The drug release performances were tested using FITC-labeled antibiotics via fluorescence spectroscopy. The nanocomplexes released the drugs more at pH 5.5 compared to pH 7.4. Antibacterial activity of the system was evaluated on various bacteria. The nanocomplex loaded with the antibiotics exhibited significantly greater efficacy against E. coli and S. aureus.