Eudragit E100/silk fibroin hybrid nanoparticles for the controlled oral delivery of amphotericin B

Aims Amphotericin B (AmB) is the first-line antifungal compound for severe fungal infections, yet it possesses high renal toxicity, low water solubility, and acidic instability in the stomach. Herein, we developed novel nanoparticles from silk fibroin with/without Eudragit E100 (FNP and FNP/EE) for the controlled oral delivery of AmB.Methods and Results The particles were formulated by two different methods of co-condensation and adsorption, which yielded comparable particle sizes of ~1500 nm (FNP-AmB) and ~800 nm (FNP/EE-AmB) and AmB entrapment efficiencies of >70%. AmB was rapidly adsorbed onto the particles by physical processes, which followed the Langmuir and Dubinin-Radushkevich isotherm models and Weber-Morris intraparticle diffusion model. The particles structures were confirmed by the FT-IR, DSC, and XRD spectra. The particles effectively protected AmB in the gastric environment, with limited AmB releases (<20%), and controlled AmB releases in the intestines, followed Korsmeyer-Peppas model. Moreover, AmB was encapsulated in partial aggregated form, with was less toxic than the free AmB; and the particles showed no hematotoxicity and adequate in vitro antifungal activity.Conclusions The particles solved the AmB limitations by (1) protecting AmB from the gastric environment, (2) controlling AmB release, (3) reducing AmB toxicity, and (4) preserving AmB efficacy.