Dados do Trabalho

Título

Development and Characterization of a Semi-Solid Base Incorporating 17-DMAG, an Hsp90 Inhibitor, as a Promising Formulation for the Control of Infection by Leishmania braziliensis, in vivo

Introdução

Leishmaniasis is caused by Leishmania and is present in 97 countries. Current treatments have limitations, such as invasive administration and severe side effects, necessitating the development of new drugs and therapies. In a non-published study, we observed that the Hsp90 inhibitor, 17-DMAG, showed anti-Leishmania and anti-inflammatory effects in vitro and in vivo, indicating its potential as a new chemotherapeutic agent. However, prolonged intraperitoneal treatment with 17-DMAG resulted in toxicity in treated animals. To reduce toxicity, incorporating drugs into semi-solid bases for topical application can be an alternative strategy.

Objetivo (s)

To evaluate the efficacy of a hydrogel containing 17-DMAG in controlling L. braziliensis infection when applied topically in vivo.

Material e Métodos

The stability of 17-DMAG in the hydrogel base was assessed at different temperatures over 90 days, and the drug release profile was characterized. Healthy BALB/c mice were exposed to different concentrations of 17-DMAG in the hydrogel or with the control hydrogel for daily application over 28 days. Histopathological analysis was conducted to evaluate potential systemic toxicity by examining the ear, liver, spleen, and kidney of the exposed animals. The efficacy of the topical formulation was also tested in BALB/c mice infected with L. braziliensis by measuring ear lesions and lymph node size.

Resultados e Conclusão

RESULTS: The topical formulation with 17-DMAG remained stable for 90 days at 4°C or 25°C, but not at 37°C. It exhibited sustained release of the drug over time. Only higher concentrations of 17-DMAG showed toxicity in the animals, which could partly be attributed to daily manipulation of ears’ mice. Treatment with 0.10 or 0.15 mg/g of 17-DMAG resulted in reduced ear lesions and accelerated healing, but no significant alteration in lymph node size was observed compared to the control groups, indicating the localized effect of the topical formulation. CONCLUSION: Topical application of 17-DMAG demonstrated partial effectiveness in treating L. braziliensis infection in vivo. Further studies should explore combining 17-DMAG with other systemically administered drugs to improve the efficacy of cutaneous leishmaniasis treatment.

Palavras-chave

Leishmaniasis; Leishmania braziliensis; 17-DMAG; Hsp90; Hydrogel; Topical treatment.

Agradecimentos

IGM (Fiocruz BA); PgBSMI; CAPES; CNPq; FAPESB; INOVA; Innovative products, 2nd round.