Phenylboronic acid-installed poly(isobutene-alt-maleic anhydride) polymeric micelles for pH-dependent release of amphotericin B

C. albicans is a common fungal pathogen causing both localized and systemic infections. The site of its infection is acidic (pH 4.5-5.5). Herein, we introduced phenylboronic acid (PBA), methoxy poly(etylene glycol) (MPEG) and ethanolamine to poly(isobutene-maleic anhydride) backbone in one pot to yield polymeric PBA (pPBA). pH-responsive amphotericin B (AMB)-loaded micelles (AMB-M) were simply formulated by mixing pPBA and AMB through a pH-responsive borate ester bond between the PBA group on pPBA and AMB's diol. The micelles showed small particle size and high AMB loads with low AMB aggregates. At pH 5.5, break of borate bond promoted drug release, which caused good in vitro antifungal activity, biofilm inhibition and cell membrane damage of AMB-M when compared with commercial AMB injection (AMB-I) and itself at physiological pH. AMB-M, like AMB-I at different pHs, damaged cell membrane integrity and reduced expression level of lipase and proteinase to a certain degree. In vivo experiments confirmed that the AMB-M exhibited good in vivo activity, improvement in macrophage function as well as a lower renal toxicity in comparison to AMB-I. The micellar platform is a promising pH-sensitive AMB delivery system to improve non-specific toxicities without compromise in antifungal activity.