title: Uptake of biodegradable gel-assisted LBL nanomatrix by Leishmania donovani-infected macrophages.
abstract: 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 <or=1.9-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.
authors.affiliation: Pharmaceutics Division, Central Drug Research Institute, Chattar Manzil Palace, P.O. Box 173, Lucknow, UP, 226001, India.
authors.forename: Girish K
authors.initials: GK
authors.lastname: Gupta
authors.forename: Shaswat
authors.initials: S
authors.lastname: Kansal
authors.forename: Pragya
authors.initials: P
authors.lastname: Misra
authors.forename: Anuradha
authors.initials: A
authors.lastname: Dube
authors.forename: Prabhat Ranjan
authors.initials: PR
authors.lastname: Mishra
mesh_terms: D000818:Animals; D001673:Biodegradation, Environmental; D002478:Cells, Cultured; D002626:Chemistry, Pharmaceutical; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D005434:Flow Cytometry; D007893:Leishmania donovani / Q000187:drug effects*; D008264:Macrophages / Q000378:metabolism / Q000469:parasitology; D051379:Mice; D053758:Nanoparticles; D013678:Technology, Pharmaceutical
chemical_list: D004317:Doxorubicin