Article
Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Leishmania braziliensis Infection
Registro en:
SILVA, Jéssica Rebouças et al. Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Leishmania braziliensis Infection. International Journal of Nanomedicine, v. 15, p. 8659–8672, 2020.
1176-9114
Autor
Silva, Jéssica Rebouças
Tadini, Maraine Catarina
Nunes, Danielle Devequi
Mansur, Ana Luíza
Mattos, Paulo Sérgio de Morais da Silveira
Oliveira, Camila Indiani de
Formiga, Fabio Rocha
Berretta, Andresa A
Oliveira, Franciane Marquele
Borges, Valéria de Matos
Resumen
FIOCRUZ (VMB), FAPESP Grant fellowships (2015/ 15948-5, 2016/10145-4, 2016/10345-3, 2016/11116-8 and 2017/22888-4) (FMO) and by the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - Brazil (CAPES) - Finance Code 001. AAB, CIO and VMB are senior scientist fellows at the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). JRS is supported by a scholarship from CAPES. PSSM holds a fellowship from Fundação de Amparo à Pesquisa do Estado da Bahia (FAPESB). 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 AmBNLC
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.