Amphotericin B loaded ethyl cellulose nanoparticles with magnified oral bioavailability for safe and effective treatment of fungal infection

Amphotericin B is a gold standard drug used in various fungal and parasitic infection treatment. Most of the marketed formulations are administered intravenously, but show dose-dependent adverse effects i.e., nephrotoxicity and hemolysis. Oral route eliminates the toxic concern but exhibits poor bioavailability. Therefore, ethylcellulose nanoparticles (EC-NPs) have been used for magnified oral delivery of AmB, where EC provides gastrointestinal stability. These nanoparticles were synthesized by high-pressure emulsification solvent evaporation (HPESE) method and evaluated for in vitro and in vivo studies. This method yields small, monodisperse AmB-EC-NPs along with smooth surface morphology and improved encapsulation efficiency. The developed formulation showed a sustained release pattern following Higuchi diffusion kinetics along with gastric and storage stability. Aggregation study revealed that AmB was present in its monomeric form inside the biocompatible EC matrix. The antifungal result demonstrated that the MIC of AmB-EC-NPs was reduced similar to 1/3rd than AmB and Fungizone (R) at 24 h whereas it was observed similar to 1/8th at 48 h. in vivo pharmacokinetic analysis demonstrated 1.3-fold higher AUC than Fungizone (R) even at a 4.5-time lesser dose via the oral route and a similar to 15-fold rise in the bioavailability in contrast to the native AmB. The hemolytic study revealed that the developed formulation exhibited 8-fold lesser hemolysis than Fungizone (R). Furthermore, the biosafety profile of AmB-EC-NPs was ensured by the significantly lesser level of blood urea nitrogen and plasma creatinine along with the normal pattern of renal tubules in comparison to AmB and Fungizone (R). In conclusion, the results stipulated that the AmB-EC-NPs could be effective, viable and a better alternative to currently existing iv formulations, for magnified oral delivery of AmB in the treatment of fungal infection without associated adverse effects.