Copolymeric micelles overcome the oral delivery challenges of amphotericin B

Abstract

© 2020 by the authors. Licensee MDPI, Basel, Switzerland. Classified as a Biopharmaceutical Classification System (BCS) class IV drug, amphotericin B (AmB) has low aqueous solubility and low permeability leading to low oral bioavailability. To improve these limitations, this study investigated the potential of AmB‐loaded polymeric micelles (AmB‐PM) to increase intestinal absorption. AmB‐PM were prepared with polyvinyl caprolactam– polyvinyl acetate–polyethylene glycol copolymer (Soluplus®) as a polymeric carrier and used a modified solvent diffusion and microfluidics (NanoAssemblr® ) method. AmB‐PM have a mean particle size of ~80 nm and are mono‐disperse with a polydispersity index <0.2. The entrapment efficiency of AmB was up to 95% and achieved with a high drug loading up to ~20% (w/w) with a total amount of incorporated drug of 1.08 ± 0.01 mg/mL. Importantly, compared to free drug, AmB‐ PM protected AmB from degradation in an acidic (simulated gastric) environment. Viability studies in Caco‐2 cells confirmed the safety/low toxicity of AmB‐PM. In vitro cellular absorption studies confirmed that AmB‐PM increased AmB uptake in Caco‐2 cells 6‐fold more than free AmB (i.e., 25% compared with 4% within 30 min). Furthermore, the permeability of AmB across Caco‐2 monolayers was significantly faster (2‐fold) and more pronounced for AmB‐PM in comparison to free drug (3.5‐ fold increase). Thus, the developed AmB‐PM show promise as a novel oral delivery system for AmB and justifies further investigation.