Article
Solid lipid nanoparticles as a novel formulation approach for tanespimycin (17-AAG) against leishmania infections: Preparation, characterization and macrophage uptake
Registro en:
PIRES, Vinícius Couto et al. Solid lipid nanoparticles as a novel formulation approach for tanespimycin (17-AAG) against leishmania infections: Preparation, characterization and macrophage uptake. Acta Tropica, p. 1-5, 16 Mar. 2020.
0001-706X
10.1016/j.actatropica.2020.105595
Autor
Pires, Vinícius Couto
Magalhães, Carla Pires
Ferrante, Marcos
Rebouças, Juliana de Souza
Nguewa, Paul
Severino, Patrícia
Barral, Aldina Maria Prado
Veras, Patrícia Sampaio Tavares
Formiga, Fabio Rocha
Resumen
Programa de Excelência Acadêmica
– Proex (PgPat/UFBA/FIOCRUZ), INCT-MCTI/CNPq/CAPES/FAPs N°
16/2014 and grants from the Fundação de Amparo à Pesquisa do
Estado da Bahia – FAPESB and the Conselho Nacional de Pesquisa e Desenvolvimento Científico – CNPq. PSTV holds a grant from CNPq for
productivity in research (307832/2015–5). In addition, this study was
financed in part by the Coordenação de Aperfeiçoamento de Pessoal de
Nível Superior – Brasil (CAPES) – Finance Code 001. The authors also
acknowledge support from the Serviço de Microscopia Eletrônica (SME)
– FIOCRUZ/BA for TEM analysis and CIENAM/UFBA for size and zeta
potential measurements 17-N-allylamino-17-demethoxygeldanamycin (17-AAG, tanespimycin) is an inhibitor of heat shock protein 90 (Hsp90), which has been studied in the treatment of cancer such as leukemia or solid tumors. Alternatively, 17-AAG may represent a promising therapeutic agent against leishmaniasis. However, the delivery of 17-AAG is difficult due to its poor aqueous solubility. For exploring the therapeutic value of 17-AAG, we developed solid lipid nanoparticles (SLN) by double emulsion method. SLN exhibited ~100 nm, PDI < 0.2 and zeta potential ~20 mV. In addition, SLN were morphologically spherical with negligible aggregation. The entrapment efficiency of 17-AAG into the lipid matrix reached at nearly 80%. In a separate set of experiments, fluorescent SLN (FITC-labeled) showed a remarkable macrophage uptake, peaking within 2 h of incubation by confocal microscopy. Regarding the drug internalization as critical step for elimination of intracellular Leishmania, this finding demonstrates an important feature of the developed SLN. Collectively, these data indicate the feasibility of developing SLN as potential delivery systems for 17-AAG in leishmaniasis chemotherapy.