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.

Renuka Khatik, Pankaj Dwivedi, Prashant Khare, Shaswat Kansal, Anuradha Dube, Prabhat Ranjan Mishra, Anil Kumar Dwivedi

Index: Expert Opin. Drug Deliv. 11(5) , 633-46, (2014)

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Abstract

The principle objective of this study was to develop 1,2-diacyl-sn-glycero-3-phospho-l-serine (PS)-coated gelatin nanoparticles (GNPs) bearing amphotericin B (AmB) for specific targeting to the macrophages involved in visceral leishmaniasis (VL).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.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 anti-leishmanial 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 inhibitions, respectively, in Leishmania-infected hamsters (p < 0.05 for PS-AmB-GNPs versus plain AmB and AmB-GNPs versus plain AmB).The objective of the preparation was achieved and high accumulation of AmB in liver and spleen has been found, which resulted in enhanced anti-leishmanial activity.