Preparation and in vitro evaluation of amphotericin B-loaded nano-formulations for both intravenous and ophthalmic administration using 3-aminophenylboronic acid-conjugated styrene-maleic acid copolymers

Abstract

Amphotericin B (AmB) is a widely used antifungal drug. However, its insolubility in water and high toxicity pose challenges to its clinical application. The aim of this study was to improve the solubility, to reduce toxicity, and to confer albumin- and mucin-binding properties. Therefore, we developed an AmB nano-formulation (APB-SMA/AmB) using a styrene-maleic acid copolymer modified with 3-aminophenylboronic acid (APB-SMA). APB-SMA/AmB was characterized and evaluated for drug content, particle size, toxicity, antifungal activity, and albumin- and mucin-binding properties.APB-SMA contains APB molecules bound to styrene-maleic acid copolymer (SMA), which can form complexes with diols. APB-SMA/AmB exhibits a small and a large peak at approximately 330 nm and 410 nm respectively, in the UV–visible spectrum, indicating the presence of a large amount of monomeric AmB, which is less toxic than its oligomeric form. The particle size of the formulations was in the nanoscale range. APB-SMA/AmB showed reduced hemolytic activity compared with AmB and the other formulations. The antifungal activity of APB-SMA/AmB is derived from AmB, and a higher APB-SMA content in the formulation improves the therapeutic index. Furthermore, APB-SMA/AmB demonstrated in vitro albumin- and mucin-binding properties, suggesting its potential as a drug delivery system for improving in vivo blood circulation and corneal retention. In conclusion, APB-SMA/AmB is an effective water-soluble nano-formulation for fungal infections and may be applicable in both injectable and ophthalmic formulations.