Original Article: Toxicology Development, characterization, and toxicity evaluation of amphotericin B–loaded gelatin nanoparticles Manoj Nahar, MPharm, Dinesh Mishra, MPharm, Vaibhav Dubey, MPharm, Narendra Kumar Jain, PhD ⁎ Pharmaceutics Research Laboratory, Department of Pharmaceutical Science, Dr. H.S. Gour University, Sagar, India 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 N .05) in hemoglobin concentration and hematocrit. Nephrotoxicity results showed that there was a nonsignificant (P N .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. © 2008 Elsevier Inc. All rights reserved. Key words: Nanoparticles; Gelatin; Amphotericin B; Desolvation; Nephrotoxicity Administration of amphotericin B (AmB), a potent fungal agent, is limited by its pronounced side effects (e.g., chills, fever, nausea, hemolytic toxicity, and nephrotoxicity). 1 Conventional micellar solutions of AmB with deoxycholate (Fungizone) has been reported to cause serious nephro- toxicity. 2 The alternate novel lipid-based nanoparticulate formulations, including liposomes (AmBisome), AmB-lipid complex (Abelcet), and AmB colloidal dispersion (Ampho- cil), have been developed to enhance the therapeutic index and to reduce the hemolytic and nephrotoxic side effects, but are quite expensive. 3 Recently, low-priced AmB disc formulations containing cationic lipid dioctadecyldimethyl have been developed, but such formulations have been reported to possess low drug-loading capacity. 4,5 Moreover, AmB is the drug of choice for diseases such as visceral leishmaniasis wherein long-term infusion is needed and that require hospitalization, increased cost, and poor patient compliance. All these factors warrant the need of developing an alternative drug carrier, which may provide safe, effective, and controlled delivery of AmB. Nanoparticulate carriers have always been attractive on account of their size and capacity for spatial and temporal controlled delivery of bioactives. 6 Nanoparticles of various polymers like poly(lactide-co- glycolide), poly(ɛ-caprolactone), and more recently chito- san-dextran with AmB have been investigated. 7-10 Gelatin nanoparticles (GNPs) have recently been developed to offer one good viable option because of their low cost, biocompatibility, biodegradability, low antigenicity, and applications in several parenteral formulations. 11 GNPs Available online at www.sciencedirect.com Nanomedicine: Nanotechnology, Biology, and Medicine 4 (2008) 252 – 261 www.nanomedjournal.com Received 11 December 2007; accepted 24 March 2008. The authors are thankful to the Indian Council of Medical Research, New Delhi for financial support. ⁎ Corresponding author. Department of Pharmaceutical Sciences, Dr. H. S. Gour University, Sagar 470003, India. E-mail address: jnarendr@yahoo.co.in (N.K. Jain). 1549-9634/$ – see front matter © 2008 Elsevier Inc. All rights reserved. doi:10.1016/j.nano.2008.03.007 Please cite this article as: M. Nahar, D. Mishra, V. Dubey, N.K. Jain, Development, characterization, and toxicity evaluation of amphotericin B–loaded gelatin nanoparticles. Nanomedicine: NBM 2008;4:252-261, doi:10.1016/j.nano.2008.03.007.