Development, characterization, and toxicity evaluation of amphotericin B–loaded gelatin nanoparticles

Abstract 

Our aim in the present investigation was to develop a nanoparticulate carrier of amphotericin B (AmB) for controlled delivery as well as reduced toxicity. Nanoparticles of different gelatins (GNPs) (type A or B) were prepared by two-step desolvation method and optimized for temperature, pH, amount of cross-linker, and theoretical drug loading. AmB-loaded GNPs were characterized for size, polydispersity index (PI), shape, morphology, surface charge, drug release, and hemolysis. The developed GNPs (GNP_A300) were found to be of nanometric size (213 ± 10 nm), having low PI (0.092 ± 0.015) and good entrapment efficiency (49.0 ± 2.9%). All GNPs showed biphasic release characterized by an initial burst followed by controlled release. The in vivo hematological toxicity results suggest nonsignificant reduction (P > .05) in hemoglobin concentration and hematocrit. Nephrotoxicity results showed that there was a nonsignificant (P > .05) increase in blood urea nitrogen and serum creatinine levels. The results confirm that developed GNPs could optimize AmB delivery in terms of cost and safety, and type A gelatin with bloom number 300 was found suitable for such preparation.

Key words: Nanoparticles, Gelatin, Amphotericin B, Desolvation, Nephrotoxicity