Development and characterization of target-driven nanotechnology based drug for Leishmaniasis treatment

• Grant number: 17/22888-4
• Support Opportunities: Research Grants - Innovative Research in Small Business - PIPE
• Start date: June 01, 2018
• End date: August 31, 2020
• Field of knowledge: Health Sciences - Pharmacy - Pharmaceutical Technology
• Principal Investigator: Franciane Marquele de Oliveira
• Grantee: Franciane Marquele de Oliveira
• Company: Eleve Science Pesquisa e Desenvolvimento Ltda
• CNAE: Pesquisa e desenvolvimento experimental em ciências físicas e naturais
• City: Ribeirão Preto
• Associated researchers: Anderson Rodrigo Moraes de Oliveira ; CAMILA INDIANI DE OLIVEIRA ; Denise Crispim Tavares Barbosa ; Eduardo Barbosa Coelho ; Jéssica Rebouças Silva ; Maraine Catarina Tadini ; Nayara Cristina Perez de Albuquerque ; Valeria de Matos Borges
• Associated research grant: 15/15948-5 - Development and characterization of a nanomedicine, target driven, to leishmaniasis treatment, AP.PIPE
• Associated scholarship(s): 19/12241-9 - Validation of the quantification method of Anf B in pharmaceutical forms, BP.TT; 19/00972-9 - Optimization of a sample preparation technique for Amphotericin B extraction from plasma and rat tissues: part II pharmacokinetic evaluation and tissue distribution of Amphotericin B, BP.TT; 18/16065-8 - Development and characterization of pharmaceutical forms to CLN-Anf administration, BP.TT; + associated scholarships 18/13827-4 - Validation of the quantification method of Anf B in pharmaceutical forms, BP.TT; 18/14539-2 - Optimization of a sample preparation technique for Amphotericin B extraction from plasma and rat tissues - part I pharmacokinetic evaluation and tissue distribution of Amphotericin B, BP.TT; 18/11584-7 - Development and characterization of target-driven nanotechnology based drug for Leishmaniasis treatment, BP.PIPE - associated scholarships

Abstract

Leishmaniasis is a group of tropical diseases caused by several species of protozoan parasites belonging to the genus Leishmania. WHO data show that Leishmaniasis reaches 12 million people in 88 countries worldwide with about 1.3 million new cases annually. Treatment for leishmaniasis is based on pentavalent antimonials, mainly sodium stibogluconate (Pentostam®) and N-methylglucamine antimoniate (Glucantime®), which have been used since 1940. In resistant cases, other drugs such as pentamidine, amphotericin B and paromomycin were reported as a second option, despite their high toxicity. These drugs are administered parenterally in prolonged dosing schedules (at least 20 days), are toxic and not always effective, leading to ineffective treatment. In addition, the resistance of the strains, the presence of other associated diseases and mainly the low selectivity are reported. The development of a new antiparasitic constitutes a scientific and technological challenge, especially because it must be able to reach Leishmania within the phagocytosome of infected macrophages that may now be in the dermal layer of the deep skin in the case of American cutaneous leishmaniasis in liver cells, spleen in visceral leishmaniasis (VL). In view of the range of applicability and success that nanostructured systems can bring to various treatments, there are several reports of its application including for leishmaniasis. Different studies have reported the importance of lipid-based carriers such as solid lipid nanoparticles (NLS) and nanostructured lipid carriers (CLN) because of the various advantages inherent in nanoparticulate systems in general, such as promoting drug stability, controlled release, (ii) incorporation of both lipophilic and hydrophilic drugs, (iii) industrial staging, and especially (iv) transportation through the lymphatic system after oral administration, promoting drug absorption. Additionally, it is still important to emphasize the possibility of obtaining systems directed to the infected tissue through the modulation of its composition. In this scenario, the possibility of using Nanoparticulate Lipid Systems (NLS and CLN) as a plausible alternative to promote the absorption of Anf B orally administered for treatment of LV or topical route for treatment of American tegumentary leishmaniasis (LTA) with release. We believe that obtaining nanomedications with topical and oral application are characterized as a highly promising proposal that can provide many benefits for patients with leishmaniasis. Thus, oral and / or topical administration of Anf B is an attractive idea as it has the potential to eliminate the acute toxicity associated with intravenous drug administration, reduce and control subacute side effects (renal toxicity), substantially reduce costs associated with treatment, improve quality of life for patients, and enable therapy to reach developing nations. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

REBOUCAS-SILVA, JESSICA; TADINI, MARAINE CATARINA; DEVEQUI-NUNES, DANIELLE; MANSUR, ANA LUIZA; SILVEIRA-MATTOS, PAULO S.; DE OLIVEIRA, CAMILA I.; FORMIGA, FABIO R.; BERRETTA, ANDRESA A.; MARQUELE-OLIVEIRA, FRANCIANE; BORGES, VALERIA M.. Evaluation of in vitro and in vivo Efficacy of a Novel Amphotericin B-Loaded Nanostructured Lipid Carrier in the Treatment of Leishmania braziliensis Infection. INTERNATIONAL JOURNAL OF NANOMEDICINE, v. 15, p. 8659-8672, 2020. (15/15948-5, 17/22888-4, 16/10145-4)

TADINI, MARAINE CATARINA; FERNANDES, FERNANDA SANTOS; OZELIN, SAULO DUARTE; SANTOS DE MELO, MATHEUS REIS; MANSUR, ANA LUIZA; DE TOLEDO, THAIS BUENO; PEREZ DE ALBUQUERQUE, NAYARA CRISTINA; TAVARES, DENISE CRISPIM; MARQUELE-OLIVEIRA, FRANCIANE; MORAES DE OLIVEIRA, ANDERSON RODRIGO. Pharmacokinetic study of AmB-NP-GR: A new granule form with amphotericin B to treat leishmaniasis and fungal infections. European Journal of Pharmaceutical Sciences, v. 173, p. 9-pg., 2022-03-28. (17/22888-4, 14/50945-4, 18/07534-4)

TADINI, MARAINE CATARINA; BALLESTERO, GIULIA; PEROVANI, ICARO SALGADO; DE ALBUQUERQUE, NAYARA CRISTINA PEREZ; FORTE, ANA LUIZA AGUILERA; MARQUELE-OLIVEIRA, FRANCIANE; DE OLIVEIRA, ANDERSON RODRIGO MORAES. Predicting absorption of amphotericin B encapsulated in a new delivery system by an in vitro Caco-2 cell model. JOURNAL OF DRUG DELIVERY SCIENCE AND TECHNOLOGY, v. 71, p. 7-pg., 2022-04-26. (17/22888-4, 18/07534-4)