In vitro evaluation of surface functionalized gelatin nanoparticles for macrophage targeting in the therapy of visceral leishmaniasis

Nahar, Manoj ; Dubey, Vaibhav ; Mishra, Dinesh ; Mishra, Pradyumna K. ; Dube, Anuradha ; Jain, Narendra K. (2010) In vitro evaluation of surface functionalized gelatin nanoparticles for macrophage targeting in the therapy of visceral leishmaniasis Journal of Drug Targeting, 18 (2). pp. 93-105. ISSN 1061-186X

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Official URL: http://www.tandfonline.com/doi/full/10.3109/106118...

Related URL: http://dx.doi.org/10.3109/10611860903115290

Abstract

The present study evaluates the potential of surface functionalized gelatin nanoparticles (f-GNPs) for efficient macrophage-specific delivery of amphotericin B (AmB) in the treatment of visceral leishmaniasis (VL). Further, the effect of spacer for macrophage targeting was also evaluated. Gelatin was functionalized either through conjugation to mannose via direct coupling (mGelatin) or via PEG spacer (m-Gelatin), and the synthesis was confirmed by FTIR. AmB-loaded f-GNPs, that is, mGNPs and m-GNPs prepared from mGelatin and m-Gelatin conjugates, respectively, were characterized. In vitro concanavalin A (Con-A) agglutination assay confirmed the availability of mannose on the surface of these f-GNPs. Kinetics of cellular uptake of AmB-loaded f-GNPs by J774A.1 macrophage cells assessed through flow cytometry demonstrated a steady increase and maximum cell-associated fluorescence was observed at 4h for m-GNPs and 6 h for m-GNPs. Measurement of cytotoxicity using Annexin-V–FITC/PI apoptosis assay delineated marginal changes (7–9%) in treated macrophages following 48 h incubation, establishing the safety of f-GNPs. m-GNPs showed a 5.4-fold reduction in IC50 in comparison with plain AmB suggesting significant enhancement of antileishmanial activity. Our results indicate that f-GNPs could be a promising carrier for specific delivery of AmB to macrophages for effective treatment of VL. Furthermore, spacer contributed significantly in reducing the cytotoxicity as well as increasing the uptake and activity of f-GNPs.

Item Type:Article
Source:Copyright of this article belongs to Informa Healthcare.
Keywords:Mannosylated Gelatin; Nanoparticles; Macrophages; Amphotericin B; J774A.1 Cell; Leishmaniasis
ID Code:101800
Deposited On:11 Mar 2017 15:15
Last Modified:11 Mar 2017 15:15

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