LUIZ FELIPE DOMINGUES PASSERO
Projetos de Pesquisa
Unidades Organizacionais
LIM/50 - Laboratório de Patologia das Moléstias Infecciosas, Hospital das Clínicas, Faculdade de Medicina
7 resultados
Resultados de Busca
Agora exibindo 1 - 7 de 7
- Topical buparvaquone nano-enabled hydrogels for cutaneous leishmaniasis(2020) LALATSA, Aikaterini; STATTS, Larry; JESUS, Jessica Adriana de; ADEWUSI, Olivia; DEA-AYUELA, Maria Auxiliadora; BOLAS-FERNANDEZ, Francisco; LAURENTI, Marcia Dalastra; PASSERO, Luiz Felipe Domingues; SERRANO, Dolores R.Leishmaniasis is a neglected disease presenting cutaneous, mucosal and visceral forms and affecting an estimated 12 million mostly low-income people. Treatment of cutaneous leishmaniasis (CL) is recommended to expedite healing, reduce risk of scarring, prevent parasite dissemination to other mucocutaneous (common with New World species) or visceral forms and reduce the chance of relapse, but remains an unmet need. Available treatments are painful, prolonged (> 20 days) and require hospitalisation, which increases the cost of therapy. Here we present the development of optimised topical self-nanoemulsifying drug delivery systems (SNEDDS) loaded with buparvaquone (BPQ, a hydroxynapthoquinone from the open Malaria Box) for the treatment of CL from New World species. The administration of topical BPQ-SNEDDS gels for 7 days resulted in a reduction of parasite load of 99.989 +/- 0.019% similar to the decrease achieved with intralesionally administered Glucantime (R) (99.873 +/- 0.204%) in a L. amazonensis BALB/c model. In vivo efficacy was supported by ex vivo permeability and in vivo tape stripping studies. BPQ-SNEDDS and their hydrogels demonstrated linear flux across non-infected CD-1 mouse skin ex vivo of 182.4 +/- 63.0 mu g cm(-2) h(-1) and 57.6 +/- 10.8 mu g cm(-2 )h(-1) respectively localising BPQ within the skin in clinically effective concentrations (227.0 +/- 45.9 mu g and 103.8 +/- 33.8 mu g) respectively. These levels are therapeutic as BPQ-SNEDDS and their gels showed nanomolar in vitro efficacy against L. amazonensis and L. braziliensis amastigotes with excellent selectivity index toward parasites versus murine macrophages. In vivo tape stripping experiments indicated localisation of BPQ within the stratum corneum and dermis. Histology studies confirmed the reduction of parasitism and indicated healing in animals treated with BPQ-SNEDDS hydrogels. These results highlight the potential clinical capability of nano-enabled BPQ hydrogels towards a non-invasive treatment for CL.
- Evaluation of in vitro activity and ultrastructural changes in Leishmania amazonensis caused by sesquiterpene lactones from Calea pinnatifida (Asteraceae)(2016) SARTORELLI, P.; YOSHINAGA, M. L.; FERREIRA, M. J. P.; LAGO, J. H. G.; PASSERO, L. F. D.
- In Vivo Antileishmanial Activity of Plant-Based Secondary Metabolites(2013) PASSERO, Luiz Felipe Domingues; LAURENTI, Marcia D.; SANTOS-GOMES, Gabriela; CAMPOS, Bruno Luiz Soares; SARTORELLI, Patricia; LAGO, Joao Henrique G.
- Evaluation of anti-inflammatory activity of derivatives from aerial parts of Baccharis uncinella(2011) ZALEWSKI, Cynthia A.; PASSERO, Luiz Felipe D.; MELO, Alexis S. R. B.; CORBETT, Carlos Eduardo P.; LAURENTI, Marcia D.; TOYAMA, Marcos H.; TOYAMA, Daniela O.; ROMOFF, Paulete; FAVERO, Oriana A.; LAGO, Joao Henrique G.Context: Species of Baccharis exhibit antibiotic, antiseptic, and wound-healing properties, and have been used in the traditional medicine of South America for the treatment of inflammation, headaches, diabetes, and hepatobiliary disorders. Objective: To investigate the anti-inflammatory activity of organic phases from EtOH extract of the aerial parts of Baccharis uncinella DC (Asteraceae). Materials and methods: The crude EtOH extract from the aerial parts of B. uncinella was subjected to partition procedures and the corresponding CH(2)Cl(2) and EtOAc phases were subjected to several chromatographic separation procedures. Thus, these phases and their purified compounds were assayed for evaluation of anti-inflammatory activity. Results: The CH(2)Cl(2) phase from EtOH extract from B. uncinella contained two triterpenoids (oleanolic and ursolic acids) and one flavonoid (pectolinaringenin), whereas the respective EtOAc phase showed to be composed mainly by two phenylpropanoid derivatives (caffeic and ferulic acids). The CH(2)Cl(2) and EtOAc phases as well as their isolated compounds exhibited anti-inflammatory effects against inflammatory reactions induced by phospholipase A2 (from Crotalus durissus terrificus venom) and by carrageenan. Discussion and conclusion: The results suggested that the components obtained from partition phases of EtOH extract of B. uncinella could represent lead molecules for the development of anti-inflammatory agents. Additionally, the results confirmed the use of Baccharis genus in the traditional medicine of South America for the treatment of inflammation and other heath disorders. To date, the present work describes for the first time the anti-inflammatory effects of compounds isolated from B. uncinella.
- Antileishmanial activity evaluation of adunchalcone, a new prenylated dihydrochalcone from Piper aduncum L.(2014) PICOLO, Camilla R. Dal; BEZERRA, Mariana P.; GOMES, Kaio S.; PASSERO, Luiz Felipe D.; LAURENTI, Marcia D.; MARTINS, Euder Glendes A.; SARTORELLI, Patricia; LAGO, Joao Henrique G.Bioactivity-guided fractionation of EtOH extract from the leaves of Piper aduncum L. (Piperaceae) afforded a new dihydrochalcone, named adunchalcone. Its structure was elucidated on the basis of their spectroscopic data, primarily NMR and MS. Adunchalcone was evaluated against promastigote forms of Leishmania (L.) amazonensis, L. (V.) braziliensis, L. (V.) shawl, and L. (L.) chagasi and displayed 50% effective concentrations (EC50) of 11.03, 26.70, and 11.26 mu M, as well as selective indexes of 4.86, 2.01, 4.76 and 0.50, respectively. This compound was also tested against intracellular forms of L. (L.) amazonensis, displaying weak activity, in comparison to reference drug amphotericin B. However, despite reduced effect of adunchalcone against amastigotes of L. (L.) amazonensis, this work opens the perspective to use this particular molecule as a scaffold for the design of novel and selective drug candidates for neglected diseases, mainly leishmaniasis.
- Mechanistic Insights into the Leishmanicidal and Bactericidal Activities of Batroxicidin, a Cathelicidin-Related Peptide from a South American Viper (Bothrops atrox)(2021) DEMATEI, Anderson; NUNES, Joao B.; MOREIRA, Daniel C.; JESUS, Jessica A.; LAURENTI, Marcia D.; MENGARDA, Ana C. A.; VIEIRA, Maria Silva; AMARAL, Constanca Pais do; DOMINGUES, Marco M.; MORAES, Josue de; PASSERO, Luiz F. D.; BRAND, Guilherme; BESSA, Lucinda J.; WIMMER, Reinhard; KUCKELHAUS, Selma A. S.; TOMAS, Ana M.; SANTOS, Nuno C.; PLACIDO, Alexandra; EATON, Peter; LEITE, Jose Roberto S. A.Snake venoms are important sources of bioactive molecules, including those with antiparasitic activity. Cathelicidins form a class of such molecules, which are produced by a variety of organisms. Batroxicidin (BatxC) is a cathelicidin found in the venom of the common lancehead (Bothrops atrox). In the present work, BatxC and two synthetic analogues, Bab(C(C-2.15Phe) and BabcC(C-2.14Phe)des-Phe1, were assessed for their microbicidal activity. All three peptides showed a broad-spectrum activity on Gram-positive and -negative bacteria, as well as promastigote and amastigote forms of Leishmania (Leishmania) amazonensis. Circular dichroism (CD) and nuclear magnetic resonance (NMR) data indicated that the three peptides changed their structure upon interaction with membranes. Biomimetic membrane model studies demonstrated that the peptides exert a permeabilization effect in prokaryotic membranes, leading to cell morphology distortion, which was confirmed by atomic force microscopy (AFM). The molecules considered in this work exhibited bactericidal and leishmanicidal activity at low concentrations, with the AFM data suggesting membrane pore formation as their mechanism of action. These peptides stand as valuable prototype drugs to be further investigated and eventually used to treat bacterial and protozoal infections.
- Repurposing Butenafine as An Oral Nanomedicine for Visceral Leishmaniasis(2019) BEZERRA-SOUZA, Adriana; FERNANDEZ-GARCIA, Raquel; RODRIGUES, Gabriela F.; BOLAS-FERNANDEZ, Francisco; LAURENTI, Marcia Dalastra; PASSERO, Luiz Felipe; LALATSA, Aikaterini; SERRANO, Dolores R.Leishmaniasis is a neglected tropical disease affecting more than 12 million people worldwide, which in its visceral clinical form (VL) is characterised by the accumulation of parasites in the liver and spleen, and can lead to death if not treated. Available treatments are not well tolerated due to severe adverse effects, need for parenteral administration and patient hospitalisation, and long duration of expensive treatments. These treatment realities justify the search for new effective drugs, repurposing existing licensed drugs towards safer and non-invasive cost-effective medicines for VL. In this work, we provide proof of concept studies of butenafine and butenafine self-nanoemulsifying drug delivery systems (B-SNEDDS) against Leishmania infantum. Liquid B-SNEDDS were optimised using design of experiments, and then were spray-dried onto porous colloidal silica carriers to produce solid-B-SNEDDS with enhanced flow properties and drug stability. Optimal liquid B-SNEDDS consisted of Butenafine:Capryol 90:Peceol:Labrasol (3:49.5:24.2:23.3 w/w), which were then sprayed-dried with Aerosil 200 with a final 1:2 (Aerosil:liquid B-SNEDDS w/w) ratio. Spray-dried particles exhibited near-maximal drug loading, while maintaining excellent powder flow properties (angle of repose <10 degrees) and sustained release in acidic gastrointestinal media. Solid-B-SNEDDS demonstrated greater selectivity index against promastigotes and L. infantum-infected amastigotes than butenafine alone. Developed oral solid nanomedicines enable the non-invasive and safe administration of butenafine as a cost-effective and readily scalable repurposed medicine for VL.