| Texto completo | |
| Autor(es): |
Reboucas-Silva, Jessica
;
Tadini, Maraine Catarina
;
Devequi-Nunes, Danielle
;
Mansur, Ana Luiza
;
Silveira-Mattos, Paulo S.
;
de Oliveira, Camila I.
;
Formiga, Fabio R.
;
Berretta, Andresa A.
;
Marquele-Oliveira, Franciane
;
Borges, Valeria M.
Número total de Autores: 10
|
| Tipo de documento: | Artigo Científico |
| Fonte: | INTERNATIONAL JOURNAL OF NANOMEDICINE; v. 15, p. 14-pg., 2020-01-01. |
| Resumo | |
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 similar to 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-alpha 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. (AU) | |
| Processo FAPESP: | 15/15948-5 - Desenvolvimento e caracterização de medicamento de base nanotecnológica, alvo-dirigido, para tratamento de leishmaniose |
| Beneficiário: | Franciane Marquele de Oliveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE |
| Processo FAPESP: | 16/10345-3 - Validação do método de quantificação da Anf B em Sistemas Nanopartículados baseados em lipídeos |
| Beneficiário: | Ana Maria de Freitas Pinheiro |
| Modalidade de apoio: | Bolsas no Brasil - Programa Capacitação - Treinamento Técnico |
| Processo FAPESP: | 16/11116-8 - Obtenção de sistemas nanoparticulados baseados em lipídeos e estudo de segurança em fibroblastos in vitro |
| Beneficiário: | Maraine Catarina Tadini |
| Modalidade de apoio: | Bolsas no Brasil - Programa Capacitação - Treinamento Técnico |
| Processo FAPESP: | 17/22888-4 - Desenvolvimento e caracterização de medicamento de base nanotecnológica, alvo-dirigido, para tratamento de Leishmaniose |
| Beneficiário: | Franciane Marquele de Oliveira |
| Modalidade de apoio: | Auxílio à Pesquisa - Pesquisa Inovativa em Pequenas Empresas - PIPE |
| Processo FAPESP: | 16/10145-4 - Desenvolvimento e caracterização de medicamento de base nanotecnológica, alvo-dirigido, para tratamento de leishmaniose |
| Beneficiário: | Franciane Marquele de Oliveira |
| Modalidade de apoio: | Bolsas no Brasil - Pesquisa Inovativa em Pequenas Empresas - PIPE |