期刊
INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
卷 105, 期 -, 页码 625-637出版社
ELSEVIER
DOI: 10.1016/j.ijbiomac.2017.07.076
关键词
Chitosan; Miltefosine; Combination therapy
资金
- Council of Scientific and Industrial Research (CSIR), New Delhi, India
- CSIR, new Delhi, India [ESC 0103]
- Department of Biotechnology, New Delhi India [GAP 0220]
Lipid nanoparticles are stable, biodegradable and biocompatible carriers offering excellent therapeutic efficacy. Here, a novel effort has been made to develop Miltefosine (HePC-hexadecylphosphocholine) stabilized chitosan anchored nanostructured lipid carriers (NLC) of Amphotericin B (AmB) as co-delivery vehicle to enhance killing of L. donovani. The entrapment efficiency of AmB was achieved upto 85.3% for HePC-AmB-CNLCs with mean particle size of 150.8 +/- 8.4nm, and zeta potential value of +28.2 +/- 1.1 mV, respectively. The cumulative amount of AmB released at even after the 24h was less than 65% from HePC-AmB-CNLCs and Tween-80-AmB-CNLCs. Intravenous administration of HePC-AmB-CNLCs revealed the significantly increased localization of AmB in both liver and spleen when estimated. FACS study represented enhanced uptake of FITC-HePC-CNLCs over FITC-HePC-NLCs in j774A.1 cell lines. Highly significant in vitro and in vivo anti-leishmanial activity (p <0.05 compared with Tween 80-AmB-CNLCs) was observed with HePC-AmB-CNLCs when tested against VL in Leishmania donovani-infected hamsters. The haemolysis and cytotoxicity studies showed the safety of HePC-AmB-CNLCs and Tween 80-AmBCNLCs. The findings suggested that it would be preferable to deliver Amathrough HePC stabilized chitosan anchored nanostructured lipid carriers for rapid and effective treatment with decreased adverse effects. (C) 2017 Elsevier B.V. All rights reserved.
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