Lis Marie Monteiro1, Raimar Löbenberg2, Nikoletta Fotaki3, Gabriel Lima Barros de Araújo1, Paulo Cesar Cotrim4, Nádia Bou-Chacra5. 1. Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. 2. Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB, Canada. 3. Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath, United Kingdom. 4. Seroepidemiology, Cellular and Molecular Immunology Laboratory - Institute of Tropical Medicine, University of São Paulo, São Paulo, Brazil. 5. Department of Pharmacy, Faculty of Pharmaceutical Sciences, University of São Paulo, São Paulo, Brazil. Electronic address: chacra@usp.br.
Abstract
OBJECTIVES: This study aimed to describe the preparation and in vitro evaluation of a surface-modified nanostructured lipid carrier (NLC) using chitosan and dextran for co-delivery of buparvaquone (BPQ) and polymyxin B (PB) against leishmaniasis. METHODS: The NLC was prepared using high-pressure homogenisation. Polymyxin B binding and surface modification with biopolymers were achieved by electrostatic interaction. In vitro cytotoxicity was assessed in mouse peritoneal macrophages, and leishmanicidal activity in amastigotes of Leishmania infantum. RESULTS: The performance attributes of BPQ-NLC, BPQ-NLC-PB[A-] (anionic) and BPQ-NLC-PB[C+] (cationic) were respectively: Z-average 173.9 ± 1.6, 183.8 ± 4.5 and 208.8 ± 2.6 nm; zeta potential -19.6 ± 1.5, -20.1 ± 1.1 and 31.1 ± 0.8 mV; CC50 583.4 ± 0.10, 203.1 ± 0.04 and 5.7 ± 0.06 μM; IC50 229.0 ± 0.04, 145.7 ± 0.04 and 150.5 ± 0.02 nM. The NLC in vitro leishmanicidal activity showed up to 3.1-fold increase when compared with free BPQ (P < 0.05, α = 0.05). CONCLUSIONS: The developed NLC proved to be a promising formulation with which to overcome the drawbacks of current leishmaniasis treatment by the co-delivery of two alternative drugs and a macrophage targeting modified surface.
OBJECTIVES: This study aimed to describe the preparation and in vitro evaluation of a surface-modified nanostructured lipid carrier (NLC) using chitosan and dextran for co-delivery of buparvaquone (BPQ) and polymyxin B (PB) against leishmaniasis. METHODS: The NLC was prepared using high-pressure homogenisation. Polymyxin B binding and surface modification with biopolymers were achieved by electrostatic interaction. In vitro cytotoxicity was assessed in mouse peritoneal macrophages, and leishmanicidal activity in amastigotes of Leishmania infantum. RESULTS: The performance attributes of BPQ-NLC, BPQ-NLC-PB[A-] (anionic) and BPQ-NLC-PB[C+] (cationic) were respectively: Z-average 173.9 ± 1.6, 183.8 ± 4.5 and 208.8 ± 2.6 nm; zeta potential -19.6 ± 1.5, -20.1 ± 1.1 and 31.1 ± 0.8 mV; CC50 583.4 ± 0.10, 203.1 ± 0.04 and 5.7 ± 0.06 μM; IC50 229.0 ± 0.04, 145.7 ± 0.04 and 150.5 ± 0.02 nM. The NLC in vitro leishmanicidal activity showed up to 3.1-fold increase when compared with free BPQ (P < 0.05, α = 0.05). CONCLUSIONS: The developed NLC proved to be a promising formulation with which to overcome the drawbacks of current leishmaniasis treatment by the co-delivery of two alternative drugs and a macrophage targeting modified surface.
Authors: Luiza F O Gervazoni; Gabrielle B Barcellos; Taiana Ferreira-Paes; Elmo E Almeida-Amaral Journal: Front Chem Date: 2020-11-23 Impact factor: 5.221