Miltefosine loaded albumin microparticles for treatment of visceral leishmaniasis: formulation development and in vitro evaluation

Introduction Visceral leishmaniasis (VL) is one of the fatal parasitic diseases, currently threatening 500,000 new cases worldwide each year. The major front line drugs available for treating VL are toxic and develop resistance due to their long treatment regimen. With this assumption, present work has been designed to formulate miltefosine (MF) as microparticulate drug delivery system to target macrophages where leishmania parasite resides. Methodology MF is formulated using albumin as carrier and spray drying as method for the preparation of microparticles of desired size (≤6 µm) for intravenous administration. Microspheres were characterized morphologically and evaluated for particle size, product yield, and for drug polymer interaction. The ability of macrophages to phagocytosis these microspheres were investigated in RAW 264.7 cell line. In vitro hemolysis study was carried out to determine hemotoxicity of prepared microsphere formulation. Results The average size of the prepared microspheres were found to be nearly 3 µm with most of particles in the range of 2–5 µm. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) confirmed no significant chemical interaction between the albumin and MF. Uptake study in macrophage cell line confirmed the targetability of prepared microspheres to macrophages. In vitro hemolysis study indicated reduced hemotoxicity and suitability of prepared microspheres for parenteral administration. Conclusions MF loaded microspheres of desired size were prepared successfully using spray drying method with thermal stabilization. In vitro hemolysis and uptake studies confirmed the suitability of prepared microspheres for targeting macrophages with reduced hemotoxicity.