Formulation and In vitro Evaluation of Nystatin-loaded Albumin Microparticles for the Treatment of Leishmaniosis

Background: The current treatments of leishmaniosis are far from ideal since they require the administration of toxic and poorly tolerated drugs that still fail to treat the intracellular infection. Micro-particles are very promising drug carriers for leishmaniosis treatment, considering the involved parasites’ life cycle and the pharmacokinetics of micro-particles. Objective: The aim of this study is to develop a novel formulation of Nystatin (Nys) that could be administered systemically and might be used for therapy of Leishmaniosis. Methods: Nys microspheres were formulated using albumin as a carrier by spray drying for the preparation of microspheres for intravenous administration. Nys microspheres were characterized morphologically and evaluated for particle size, product yield, encapsulation efficiency, and drug-polymer interaction. Anti-Leishmanial activity against Leishmania tropica was tested and the microspheres’ phagocytosis by murine macrophages was investigated. An in vitro hemolysis study was carried out for the novel formulation and for the free Nys. Results: The average size of microspheres was found to be less than 5 μm. Differential Scanning Calorimetry (DSC) and Fourier-Transform Infrared spectroscopy (FTIR) confirmed no significant interactions between albumin and Nys. The anti-leishmanial activity of Nys microspheres was higher than that for free Nys with an IC50 value of (18.1 μg/mL). Uptake study in murine macrophage confirmed the targetability of the prepared microspheres. The in vitro hemolysis study indicated reduced hemolysis and suitability of the microspheres for parenteral administration. Conclusion: Spray drying was used successfully to prepare highly loaded Nys microspheres with high anti-leishmanial activity and less hemolysis effect.