Browsing by Author "Anuradha Dude"

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Nanonization increases the antileishmanial efficacy of amphotericin B: An ex vivo approach
(Springer New York LLC, 2014) Krishna Das Manandhar; Thakur Prasad Yadav; Vijay Kumar Prajapati; Om Basukala; Ram Prasad Aganja; Anuradha Dude; Onkar Nath Shrivastav; Shyam Sundar
With widespread resistance to pentavalent antimonial in the endemic eastern terai belt of Nepal and Bihar, India, Amphotericin B deoxycholate is now the first-line antileishmanial drug for the treatment of visceral leishmaniasis (VL). However, universal occurrence of infusion-related fever and rigors with amphotericin B (AmB), occasional serious life-threatening toxicities like cardiotoxicity, anaphylaxis, hypokalemia, and nephrotoxicity are major barriers to its use in areas with limited medical facilities. Liposomal amphotericins, however, are devoid of adverse effects, high cost makes it unaffordable. We had formulated nanoparticles (10–20 nm) from amphotericin B deoxycholate (1–2 µm) applying high pressure (150 atm) milling homogenization in argon atmosphere and tested its ex vivo efficacy in Leishmania infected J774A cell line and peritoneal macrophage. The ex vivo ED50 for intracellular amastigotes in peritoneal macrophage by nanoamphotericin was 0.0027 ± 0.001 lg/mL which was significantly less (p = 0.0029) than the required dose of amphotericin B (0.0426 ± 0.003 µg/mL). Similarly, in J774A cell line, 50 % of intracellular amastigotes were cleared by 0.0038 ± 0.001 µg/mL of nano-amphotericin while the dose was a bit more for AmB (0.0196 ± 0.001 µg/mL) illustrating the significant difference (p value, 0.0122). The nanoformulation has also shown high efficacy (ED50, 0.0028–0.0035 µg/mL) in inhibition of infected macrophage count. The new formulation accumulated to spleen, the targeted organ, 7 days after inoculation of drug to the infected hamster as traced in vivo by TEM convincing it as potential drug. Given a favorable safety profile and very low cost of production contemplated, it may prove to be a feasible alternative for conventional amphotericin B. © Springer India 2014.