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

Abstract

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 mm) 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 mm with most of particles in the range of 2-5 mm. 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.

Passive targeting and lung tolerability of enoxaparin microspheres for a sustained antithrombotic activity in rats

“…In vitro Enox release study. In vitro release study was done using a membrane-less model (Rawat et al, 2008b ; Das et al, 2011 ). Ten milligrams of the selected drug loaded and plain counterpart formulae were accurately weighed and suspended in 3 mL PBS, pH 7.4.…”

Preparation of meglumine antimonate loaded albumin nanoparticles and evaluation of its anti-leishmanial activity: an in vitro assay

“…In some similar studies, albumin has also been used to prepare nano-drugs. In a study conducted by Samir Das et al (2011) to evaluate the anti-leishmanial effect of miltefosine-loaded albumin in invitro, the toxicity of the drug was reduced on the RAW264.7 macrophages, and the drug was able to target macrophages very well. In another study, the intake of paramomycin-loaded albumin by RAW264.7 macrophages was evaluated in invitro conditions and the authors mentioned that the rate of drug intake was significant, which is considered appropriate for the treatment of visceral leishmaniasis (Khan and Kumar 2011).…”

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