Navegando por Autor "Tavares, Harley da Silva"
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Item Nanoemulsion composed of 10-(4,5-dihydrothiazol-2-yl)thio)decan-1-ol), a synthetic analog of 3-alkylpiridine marine alkaloid : development, characterization, and antimalarial activity.(2020) Silva, Marina Goulart da; Cardoso, Jéssica Ferreira; Perasoli, Fernanda Barçante; Branquinho, Renata Tupinambá; Mourão, Renata Silva; Tavares, Harley da Silva; Xocaira, Maria Luiza Costa Trench; Guimarães, Daniel Silqueira Martins; Viana, Gustavo Henrique Ribeiro; Varotti, Fernando de Pilla; Silva, Gisele Rodrigues daMalaria treatment is based on a reduced number of antimalarial drugs, and drug resistance has emerged, leading to the search for new antimalarial drugs incorporated into pharmaceutical formulations. In this study, 10-(4,5- dihydrothiazol-2-yl)thio)decan-1-ol) (thiazoline), a synthetic analog of 3-alkylpiridine marine alkaloid, and a potent antimalarial substance, was incorporated into O/W nanoemulsion. This formulation was prepared by a 23 factorial design. It was characterized by globule diameter, polydispersity index, zeta potential, encapsulation efficiency, in vitro thiazoline release at pH 2 and 6.86, and accelerated stability. In vitro and in vivo antimalarial activity was determined against P. falciparum and P. berghei, respectively. Thiazoline nanoemulsion showed 248.8 nm of globule diameter, 0.236 of polydispersity index, -38.5 mV of zeta potential, 96.92% encapsulation efficiency, and it was stable for 6 months. Thiazoline release profiles differed in acidic and neutral media, but in both cases, the nanoemulsion controlled and prolonged the thiazoline delivery. Thiazoline nanoemulsion exerted in vitro antimalarial activity against the parasite (IC50 = 1.32 µM), and it significantly reduced the in vivo parasitemia for 8 days without increasing the survival time of animals. Therefore, the thiazoline nanoemulsion represents a strategy to treat malaria combining an antimalarial candidate and a new nanocarrier.Item Spiramyin-loaded PLGA implants for the treatment of ocular toxoplasmosis : development, characterization, biocompatibility, and anti-toxoplasma activity.(2021) Tavares, Harley da Silva; Cardoso, Jéssica Ferreira; Almeida, Tamires Cunha; Marques, Maria Betânia de Freitas; Mussel, Wagner da Nova; Lopes, M. C. P.; Oréfice, Rodrigo Lambert; Andrade, Silmara Nunes; Varotti, Fernando de Pilla; Silva, Glenda Nicioli da; Silva, Gisele Rodrigues daOcular toxoplasmosis is the major cause of infectious posterior uveitis worldwide, inducing visual field defect and/or blindness. Despite the severity of this disease, an effective treatment is still lacking. In this study, spiramycin-loaded PLGA implants were developed aiming at the treatment of ocular toxoplasmosis. Implants were manufactured by a hot-molding technique, characterized by Fourier Transform Infrared Spectroscopy, X-Ray Diffraction, Differential Scanning Calorimetry, Scanning Electron Microscopy; evaluated in terms of ocular biocompatibility by immunofluorescence, flow cytometry, cell migration, Hen’s egg test-chorioallantoic membrane (HET-CAM) irritation test; and investigated in terms of in vitro efficacy against Toxoplasma gondii. Characterization techniques indicated that spiramycin was dispersed into the polymeric chains and both substances preserved their physical structures in implants. The HET-CAM test indicated that implants did not induce hemorrhage or coagulation, being non-irritant to the CAM. ARPE-19 cells showed viability by MTT assay, and normality in cell cycle kinetics and morphology, without stimulating cell death by apoptosis. Finally, they were highly effective against intracellular parasites without inducing human retinal pigment epithelial cell death. In conclusion, spiramycin-loaded PLGA implants represent a promising therapeutic alternative for the local treatment of ocular toxoplasmosis.Item Therapeutic alternatives for the treatment of ocular toxoplasmosis.(2020) Tavares, Harley da Silva; Silva, Gisele Rodrigues daOcular toxoplasmosis is caused by Toxoplasma gondii, inducing retinochoroiditis. It is the leading cause of infectious posterior uveitis worldwide. Its treatment is based on oral drug administration. However, the blood–ocular barrier systems make the penetration of therapeutic drug concentrations within the eye difficult, limiting the effectiveness of treatments. In this context, ocular drug delivery systems represent therapeutic alternative for the treatment of ocular toxoplasmosis. In this study, a review of clinical manifestations, diagnosis, treatment, and perspectives regarding the treatment of ocular toxoplasmosis was conducted. A search was carried out on ScienceDirect, Scopus, Web of Science, PubMed, and SciELO, and the following keywords were used: toxoplasmosis, ocular toxoplasmosis, toxoplasmic retinochoroiditis, and congenital toxoplasmosis; and Boolean operators, associated with other keywords, such as epidemiology, ocular toxoplasmosis diagnosis, ocular toxoplasmosis treatment, and ocular toxoplasmosis perspectives, were applied. In conclusion, ocular toxoplasmosis still lacks effective treatment. Therefore, it is essential to develop new molecules and/or new drug delivery systems capable of releasing therapeutic doses of anti-Toxoplasma drugs directly in the posterior segment of the eye, for an extended period, since complications resulting from the disease may shorten the productive life of individuals and may even lead to blindness.Item Vancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid to treat bacterial endophthalmitis : development, characterization, and ocular biocompatibility.(2021) Cardoso, Jéssica Ferreira; Perasoli, Fernanda Barçante; Almeida, Tamires Cunha; Marques, Maria Betânia de Freitas; Toledo, Cibele Rodrigues; Gil, Priscilla Oliveira; Tavares, Harley da Silva; Paz, Mariana Campos da; Mussel, Wagner da Nova; Magalhães, Juliana Texeira; Silva, Glenda Nicioli da; Cunha Júnior, Armando da Silva; Granjeiro, Paulo Afonso; Klibanov, Alexander M.; Silva, Gisele Rodrigues daVancomycin-loaded N,N-dodecyl,methyl-polyethylenimine nanoparticles coated with hyaluronic acid (VCMDMPEI nanoparticles/HA) were synthesized as an adjuvant for the treatment of bacterial endophthalmitis. The nanoparticles were formulated by experimental statistical design, thoroughly characterized, and evaluated in terms of bactericidal activity and both in vitro and in vivo ocular biocompatibility. The VCM-DMPEI nanoparticles/HA were 154 ± 3 nm in diameter with a 0.197 ± 0.020 polydispersity index; had a + 26.4 ± 3.3 mV zeta potential; exhibited a 93% VCM encapsulation efficiency; and released 58% of the encapsulated VCM over 96 h. VCM and DMPEI exhibited a synergistic bactericidal effect. The VCM-DMPEI nanoparticles/HA were neither toxic to ARPE-19 cells nor irritating to the chorioallantoic membrane. Moreover, the VCM-DMPEI nanoparticles/HA did not induce modifications in retinal functions, as determined by electroretinography, and in the morphology of the ocular tissues. In conclusion, the VCM-DMPEI nanoparticles/HA may be a useful therapeutic adjuvant to treat bacterial endophthalmitis.