Development of targeted 1, 2-diacyl-sn-glycero-3-phospho-L-serine coated Gelatin nanoparticles loaded with Amphotericin B for improved in vitro and in vivo effect in Leishmaniasis.

Abstract

bjective: The principle objective of this study was to develop phosphatidylserine (PS) coated gelatin nanoparticles (GNPs) bearing amphotericin B (AmB) for specific targeting to the macrophages involved in visceral leishmaniasis (VL). Method: The two step desolvation method has been used for the preparation of GNPs with AmB which was further coated with PS (PS-AmB-GNPs). The targeting potential of it was compared with uncoated AmB loaded GNPs (AmB-GNPs) for in vitro and in vivo macrophage uptake. Results: The results of flow cytometric data revealed enhanced uptake of PS-AmB-GNPs in J774A.1 macrophage cell lines compared with AmB-GNPs. In vivo organ distribution studies in Wistar rats demonstrated a significantly higher extent of accumulation of PS-AmB-GNPs compared with AmB-GNPs in macrophage-rich organs, particularly in liver and spleen. The in vivo anti-leishmanial activity of plain AmB, AmB-GNPs and PS-AmB-GNPs was tested against VL in Leishmania Donovani - infected hamsters. Highly significant antileishmanial activity (P<0.05 compared with AmB-GNPs) was observed with PS-AmB-GNPs, causing 85.3 ± 7.89% inhibition of splenic parasitic burden. AmB-GNPs and plain AmB caused only 71.0 ± 3.87 % and 50.5 ± 5.12 % parasite inhibition, respectively, in Leishmania infected hamsters (P<0.05 for PS-AmB-GNPs versus plain AmB and AmB-GNPs versus plain AmB). Conclusion: The objective of the preparation was achieved and high accumulation of AmB in Liver and spleen has been found which resulted in enhanced antileishmanial activity