Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Leishmania braziliensis Infection
Received 19 May 2020
Accepted for publication 27 August 2020
Published 5 November 2020 Volume 2020:15 Pages 8659—8672
Checked for plagiarism Yes
Review by Single anonymous peer review
Peer reviewer comments 2
Editor who approved publication: Prof. Dr. Anderson Oliveira Lobo
Jéssica Rebouças-Silva,1,2,* Maraine Catarina Tadini,3,4,* Danielle Devequi-Nunes,1,5 Ana Luíza Mansur,3 Paulo S Silveira-Mattos,1,2 Camila I de Oliveira,2,6 Fábio R Formiga,7,8 Andresa A Berretta,9 Franciane Marquele-Oliveira,3 Valéria M Borges1,2
1Laboratory of Inflammation and Biomarkers, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil; 2Postgraduate Program in Pathology, Faculty of Medicine of Bahia, Federal University of Bahia (UFBA), Salvador, Bahia, Brazil; 3Eleve Science Research and Development, Ribeirão Preto, São Paulo, Brazil; 4Department of Chemistry, Faculty of Philosophy, Sciences and Letters of Ribeirão Preto, University of São Paulo, Ribeirão Preto, SP, Brazil; 5Laboratory of Pharmaceutical Formulations, SENAI Institute of Innovation in Advanced Health Systems, Salvador, Bahia, Brazil; 6Laboratory of Vector-Borne Infectious Diseases, Gonçalo Moniz Institute, Oswaldo Cruz Foundation, Salvador, Bahia, Brazil; 7Aggeu Magalhães Institute, Oswaldo Cruz Foundation (FIOCRUZ), Recife, Pernambuco, Brazil; 8Postgraduate Program in Applied Cellular and Molecular Biology, University of Pernambuco (UPE), Recife, Pernambuco, Brazil; 9Laboratory of Research, Development and Innovation, Apis Flora Industrial e Comercial Ltda, Ribeirão Preto, São Paulo, Brazil
*These authors contributed equally to this work
Correspondence: Valéria M Borges; Franciane Marquele-Oliveira Email email@example.com; firstname.lastname@example.org
Background: Leishmaniasis is a neglected disease, and the current therapeutic arsenal for its treatment is seriously limited by high cost and toxicity. Nanostructured lipid carriers (NLCs) represent a promising approach due to high drug loading capacity, controlled drug release profiles and superior stability. Here, we explore the efficacy of a unique pH-sensitive amphotericin B-loaded NLC (AmB-NLC) in Leishmania braziliensis infection in vitro and in vivo.
Methods and Results: AmB-NLC was assessed by dynamic light scattering and atomic force microscopy assays. The carrier showed a spherical shape with a nanometric size of 242.0 ± 18.3 nm. Zeta potential was suggestive of high carrier stability (− 42.5 ± 1.5 mV), and the NLC showed ∼ 99% drug encapsulation efficiency (EE%). In biological assays, AmB-NLC presented a similar IC50 as free AmB and conventional AmB deoxycholate (AmB-D) (11.7 ± 1.73; 5.3 ± 0.55 and 13 ± 0.57 ng/mL, respectively), while also presenting higher selectivity index and lower toxicity to host cells, with no observed production of nitric oxide or TNF-α by in vitro assay. Confocal microscopy revealed the rapid uptake of AmB-NLC by infected macrophages after 1h, which, in association with more rapid disruption of AmB-NLC at acidic pH levels, may directly affect intracellular parasites. Leishmanicidal effects were evaluated in vivo in BALB/c mice infected in the ear dermis with L. braziliensis and treated with a pentavalent antimonial (Sb5+), liposomal AmB (AmB-L) or AmB-NLC. After 6 weeks of infection, AmB-NLC treatment resulted in smaller ear lesion size in all treated mice, indicating the efficacy of the novel formulation.
Conclusion: Here, we preliminarily demonstrate the effectiveness of an innovative and cost-effective AmB-NLC formulation in promoting the killing of intracellular L. braziliensis. This novel carrier system could be a promising alternative for the future treatment of cutaneous leishmaniasis.
Keywords: leishmaniasis, neglected disease, nanoparticles, drug delivery
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