Dados do Trabalho

Título

Development and Characterization of Polymeric Nanoparticles for Controlled Delivery of 17-DMAG as a Potential Treatment for Cutaneous Leishmaniasis

Introdução

Heat shock protein 90 (Hsp90) is crucial for Leishmania's life cycle. The Hsp90 inhibitor, 17-DMAG, significantly reduced lesion size, cytokine production, and parasite burden in L. braziliensis-infected mice. However, prolonged treatment led to signs of toxicity. To address this, we developed protocols to encapsulate 17-DMAG in nanoparticles for controlled and targeted release, aiming to reduce toxicity and improve efficacy in cutaneous leishmaniasis (CL) treatment.

Objetivo (s)

We aim to produce and characterize polymeric nanoparticles (NPs) containing 17-DMAG as a potential chemotherapeutic agent for CL.

Material e Métodos

We used three polymers (PLGA, PCL, and PLLA) to produce NP-PLGA, NP-PCL, and NP-PLLA, respectively. These NPs were morphologically characterized using electron microscopy. Dynamic Light Scattering (DLS) was used to assess size, polydisperse index (PdI), and charge (zeta potential-ZP). Encapsulation efficiency (%EE) of 17-DMAG in NPs was estimated via high-performance liquid chromatography (HPLC). Toxicity and efficacy evaluations focused on 17-DMAG-loaded PLGA (NP-PLGA-17-DMAG) due to its superior morphological and physicochemical properties. CC50 and IC50 values were determined by exposing uninfected BMMΦ and L. braziliensis-infected cells to various concentrations of 17-DMAG incorporated into NP-PLGA, compared to empty NP-PLGA or free 17-DMAG.

Resultados e Conclusão

Electron microscopic observations revealed that NP-PLGA-17-DMAG displayed better morphological characteristics than NP-PCL and NP-PLLA. NP-PLGA-17-DMAG exhibited lower average size, PdI, and ZP compared to the other tested NPs. NP-PLLA-17-DMAG showed a smaller average size and ZP, as well as higher %EE, compared to NP-PCL-17-DMAG. Despite these characteristics, encapsulated NP-PLGA-17-DMAG demonstrated for BMM a CC50 value 10.9 times lower, and for intracellular parasite viability, an IC50 value 3.36 times higher than those for free 17-DMAG.
NP-PLGA-17-DMAG exhibited higher toxicity and lower efficacy compared to free 17-DMAG, likely due to a lower %EE of the encapsulated compound. NP-PLLA-17-DMAG showed to be a promising nanoformulation for further evaluation.

Palavras-chave

Leishmaniasis; Leishmania braziliensis; Treatment; HSP90; Nanoparticle; 17-DMAG.

Agradecimentos

Coordination for the Improvement of Higher Education Personnel (CAPES); National Council for Scientific Research and Development (CNPq); Foundation for the Support of Research in the State of Bahia (FAPESB); INOVA; Innovative products, 2nd round.