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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

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

Expert Opin Drug Deliv. 2014 May;11(5):633-46.

PMID: 24606222

Abstract:

Objective:
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).
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 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).
Conclusion:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR4242995	1,2-Diacyl-sn-glycero-3-phospho-L-serine			Price

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