Calvo-Bacaicoa, A. (Alba)
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- Evaluation of skin permeation and retention of topical dapsone in murine cutaneous leishmaniasis lesions(2019) Sanmartin-Grijalba, C. (Carmen); Schwartz, J. (Juana); Calvo-Bacaicoa, A. (Alba); Gonzalez-Peñas, E. (Elena); Espuelas, S. (Socorro); Navarro-Blasco, I. (Iñigo); Moreno-Amatria, E. (Esther); Irache, J.M. (Juan Manuel)The oral administration of dapsone (DAP) for the treatment of cutaneous leishmaniasis (CL) is effective, although serious hematological side effects limit its use. In this study, we evaluated this drug for the topical treatment of CL. As efficacy depends on potency and skin penetration, we first determined its antileishmanial activity (IC50 = 100 ¿M) and selectivity index in vitro against Leishmania major-infected macrophages. In order to evaluate the skin penetration ex vivo, we compared an O/W cream containing DAP that had been micronized with a pluronic lecithin emulgel, in which the drug was solubilized with diethylene glycol monoethyl ether. For both formulations we obtained similar low flux values that increased when the stratum corneum and the epidermis were removed. In vivo efficacy studies performed on L. major-infected BALB/c mice revealed that treatment not only failed to cure the lesions but made their evolution and appearance worse. High plasma drug levels were detected and were concomitant with anemia and iron accumulation in the spleen. This side effect was correlated with a reduction of parasite burden in this organ. Our results evidenced that DAP in these formulations does not have an adequate safety index for use in the topical therapy of CL.
- Oral efficacy of a diselenide compound loaded in nanostructured lipid carriers in a murine model of visceral leishmaniasis(2021) Almeida, A.J. (Antonio J.); Alvarez-Galindo, J.I. (José Ignacio); Sanmartin-Grijalba, C. (Carmen); Etxebeste-Mitxeltorena, M. (Mikel); Calvo-Bacaicoa, A. (Alba); Plano-Amatriain, D. (Daniel); Gonzalez-Peñas, E. (Elena); Espuelas, S. (Socorro); Carvalheiro, M. (Manuela); Navarro-Blasco, I. (Iñigo); Moreno-Amatria, E. (Esther); Irache, J.M. (Juan Manuel)Leishmaniasis urgently needs new oral treatments, as it is one of the most important neglected tropical diseases that affects people with poor resources. The drug discovery pipeline for oral administration currently discards entities with poor aqueous solubility and permeability (class IV compounds in the Biopharmaceutical Classification System, BCS) such as the diselenide 2m, a trypanothione reductase (TR) inhibitor. This work was assisted by glyceryl palmitostearate and diethylene glycol monoethyl ether-based nanostructured lipid carriers (NLC) to render 2m bioavailable and effective after its oral administration. The loading of 2m in NLC drastically enhanced its intestinal permeability and provided plasmatic levels higher than its effective concentration (IC50). In L. infantum-infected BALB/c mice, 2m-NLC reduced the parasite burden in the spleen, liver, and bone marrow by at least 95% after 5 doses, demonstrating similar efficacy as intravenous Fungizone. Overall, compound 2m and its formulation merit further investigation as an oral treatment for visceral leishmaniasis.
- Towards improved antileishmanial therapies: delivery issues and application to berberine(Universidad de Navarra, 2021-06-14) Calvo-Bacaicoa, A. (Alba); Espuelas, S. (Socorro); Moreno-Amatria, E. (Esther)En esta tesis se investigación sobre la posible explotación del berberine como antileishmanial.