Development of Oral pH-Sensitive Eudragit L100-Functionalized Bombyx mori Silk Fibroin Nanoparticles Containing Amphotericin B: Formulations, Characterizations, In Silico

Abstract

Amphotericin B (AmB) is a poorly water-soluble drug with low oral bioavailability and high nephrotoxicity. Thus, this study developed oral AmB-loaded pH-sensitive Eudragit L100-functionalized silk fibroin nanoparticles (SF/EL-AmB) to enhance its oral bioavailability and reduce its renal toxicity. The particles were formulated using two different methods of desolvation and adsorption, followed by thorough characterizations regarding particle size, polydispersity index, zeta potential, chemical interactions, AmB entrapment efficiency, specific surface area, drug release in simulated oral conditions, and in vitro antifungal activity. The optimal formula (SF:EL ratio of 1:3 and initial AmB amount of 0.5 mg) yielded particles with average size of 577.9 nm, zeta potential of −47.9 mV, drug loading efficiency of 77.99 ± 2.35%, specific surface area of 38.969 m2/g with mostly mesopores, and moderate in vitro antifungal activity on Candida albicans with IC50 of 4.09 ± 0.21 μg/mL and MIC of 32.0 μg/mL. Analytical techniques (XRD, DSC, and FTIR) and in silico modeling confirmed that AmB was entrapped within the SF/EL nanoparticles in an amorphous molecular dispersion state via hydrogen bonding and ionic interactions between AmB and charged residues of SF, notably Lys82, Glu98, and Lys62. Interestingly, the SF/EL nanoparticles could protect AmB through the stomach acidic condition and control its release rate in the small intestine based on the formulation methods (desolvation or adsorption). Lastly, the SF/EL-AmB nanoparticles could reduce AmB aggregation forms, which theoretically links to a decrease in AmB nephrotoxicity. In conclusion, the SF/EL-AmB nanoparticles could be further investigated to become a novel product for oral AmB delivery.