Journal
AAPS PHARMSCITECH
Volume 10, Issue 4, Pages 1343-1347Publisher
SPRINGER
DOI: 10.1208/s12249-009-9334-y
Keywords
flow cytometry; layer-by-layer; Leishmania donovani; nanomatrix; visceral leishmaniasis
Categories
Funding
- Department of Science and Technology, New Delhi, India
- Indian Council of Medical Research
- Council of Scientific and Industrial Research, New Delhi, India
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The aim of this study was to develop novel gel-assisted layer-by-layer (LBL) nanomatrix with high payload of doxorubicin (DOX) and to assess its efficacy against Leishmania donovani. The biodegradable LBL nanomatrix was fabricated using LBL technique using polyions (protamine and sodium alginate) on decomposable core. The developed system was characterized in vitro in terms of layer-by-layer growth and payload efficiency. The efficacy of optimized formulations was evaluated against L. donovani strain in terms of inhibitory concentration (IC50). Uptake studies by infected macrophages were investigated both qualitatively and quantitatively using fluorescence microscopy and flow cytometry. The autogelling property subsequent to core removal inside the nanomatrix resulted in high payload efficiency of DOX (i.e., > 70%). The reversal in charge followed the same trend with additional layers, and the magnitude of the charge remained constant up to five complete bilayers of polyions. The DOX can be effectively encapsulated, delivered, and subsequently taken up by L. donovani-infected macrophage cells. The matrix is completely internalized into macrophages showing improved efficacy (IC50 of formulation is almost a parts per thousand currency sign1.9-fold as compared to plain drug, P < 0.05) against intracellular amastigotes. Having ample of opportunity to manipulate surface architecture, this system demonstrates unique platform as a low cost ideal substitute for visceral leishmaniasis to expensive lipid-based formulations.
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