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Abstract

LIPOSPHERES OF ANTIRETROVIRAL PROTEASE INHIBITORS: AN APPROACH FOR BETTER TREATMENT OF DRUG RESISTANT PARASITES AND HIV-MALARIA CO-INFECTION

Bhavsar D B, Gonarkar A B*, Nigde A, Suryawanshi P, Yeole S, Pimple S S

ABSTRACT

Parasite resistance to antimalarial drugs is a life-threatening problem, and novel agents acting on enzymes essential for parasite metabolism, such as proteases, are attractive targets for drug development. Recent studies have shown that antiretroviral protease inhibitors (ARPIs) possess some antimalarial activity by inhibiting an aspartyl protease of malaria parasite. The present study deals with the formulation of lopinavir-ritonavir lipospheres (LOP-RIT LS) to enhance their activity in the treatment of drug resistant malaria as well as a malaria human immunodeficiency virus (HIV) co-infection. LS were prepared by using hot melt homogenization method. Fourteen different formulations (F1-F14) have been prepared by varying different parameters like lipid concentration, surfactant type and surfactant concentration. The prepared formulations were investigated for particle size, surface morphology, entrapment efficiency (EE) and in-vitro drug release. Among all formulations, F9 was found to be optimized, having a particle size (140.13±0.7 NM), EE (82.39±0.41% LOP, 83.91±0.42 RIT) and extended drug release (86.45±0.43% LOP, 83.79.12±0.42% RIT). Further characterization of optimized formulation for differential scanning calorimetry (DSC) confirmed entrapment of both the drugs in LS, X-ray diffraction (XRD) revealed crystalline nature and stability studies prove stability. In case of in-vivo study, LS formulation was found superior to marketed product in its ability to suppress parasite.

Keywords: Parasite resistance, Malaria HIV co-infection, Antiretroviral protease inhibitors, lopinavir, ritonavir, lipospheres.


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