Effect of Paromomycin Loaded Solid Lipid Nanoparticle Formulation on Leishmanial Infection: In vitro and In vivo study

Abstract: Leishmaniasis, is a worldwide disease and leading to high mortality and morbidity in human populations. The drugs that are already in clinical use are limited to a number of toxic chemical compounds and the parasite drug resistance has been increased. Therefore, there is an essential need to design new anti leishmanial drug treatment strategy. One promising strategy could be developing novel delivery systems and formulations of the existing pharmaceutical ingredients to improve the drug efficacy. In the present study paromomycin sulfate (PM) has been formulated in solid lipid nanoparticles (SLN) and it’s in vitro and in vivo efficacy was investigated against L. tropica and L. major. In order to compute CC50, IC50 and EC50 of PM and PM-SLN formulations, MTT test and Parasite-Rescue-Transformation-Assay were used. SYTO Green Staining, Fluorescent Microscope Imaging and Quantitative Parasite Burden were applied for evaluation of the cell percentage infection. To determine the drug efficacy in vivo, footpad thickness and Real time PCR was assessed in infected BALB/c mice. Nitric oxide test and cytokine assay (interleukin-4 (IL-4) and gamma interferon (IFN -γ)) were performed. All together, the results show that PM loaded SLN is significantly more effective than PM for the inhibition of the parasite propagation (P<0.05) and accelerate the immune response toward healing and controlling the disease in BALB/c mice model.

Keywords:

Leishmaniasis , Solid Lipid Nanoparticle , Drug Delivery , Balb/c , IL-4 , IFN -γ