|Title||DEVELOPMENT AND EVALUATION OF MACROPHAGE TARGETED MULTIDRUG THERAPY AGAINST VISCERAL LEISHMANIASIS- IN-VIVO STUDIES|
Prachi Sharma & Dr. Swati Gupta
Apeejay Stya University, India
Co-encapsulated amphotericin B (AmB) and doxorubicin (DOX) in poly (€-caprolactone) nanoparticles (PCL-NPs) were prepared via double-emulsion solvent evaporation method. PCL-NPs were modified by coating them with macrophage-specific ligand- lectin. The surface modified and un-modified PCL-NPs were characterised for shape, size, zeta potential and entrapment efficiency. The antileishmanial activity of free and drug loaded PCL-NPs was tested in-vitro in L. donovani infected macrophage-amastigote system (J774A.1 cells), which showed higher efficacy of lectin- PCL-NPs over drug loaded PCL-NPs and free PCL-NPs. The mean particle size and mean zeta potential of drug loaded PCL-NPs were 236.7± 0.04 nm in diameter and -9.11± 3.46 mV, respectively. The entrapment efficiencies of amphotericin B and doxorubicin were 82.1 ± 1.39 and 75.20 ± 0.14%, respectively. In vivo studies were conducted in Syrian golden hamsters as per fixed protocols and the results drawn from in vivo studies displayed substantial reduction in leishmanial parasite load for lectin-PCL-NPs over drug loaded PCL-NPs and free PCL-NPs. The in-vivo organ distribution studies in albino rats established that degree of accumulation of PCL-NPs entrapped combination of AmB and DOX in macrophage rich organs was considerably high when compared against free PCL-NPs. The rate and degree of accumulation were found to increase further on ligand anchoring. The in-vivo antileishmanial activity of the lectin coated PCL-NPs were found to be superior as compared to PCL-NPs against VL in L. donovani infected hamsters. The proposed formulations, PCL-NPs and lectin-PCL-NPs confirmed remarkable potential for passive and active intra-macrophage targeting respectively and the strategy could be a best alternative to the presently existing drug regimens of VL.