Research Grants 20/16215-0 - Tratamento de doenças, Tratamento do câncer - BV FAPESP
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Lipid core nanoparticles (LDE) as vehicles of chemotherapeutic agents: a new standard for the medical therapeutics

Grant number: 20/16215-0
Support Opportunities:Research Projects - Thematic Grants
Field of knowledge:Health Sciences - Medicine - Medical Clinics
Principal Investigator:Raul Cavalcante Maranhao
Grantee:Raul Cavalcante Maranhao
Host Institution: Instituto do Coração Professor Euryclides de Jesus Zerbini (INCOR). Hospital das Clínicas da Faculdade de Medicina da USP (HCFMUSP). Secretaria da Saúde (São Paulo - Estado). São Paulo , SP, Brazil
Pesquisadores principais:
Raul Dias dos Santos Filho
Associated researchers:Aleksandra Tiemi Morikawa ; Carmen Guilherme Christiano de Matos Vinagre ; Carolina Graziani Vital ; Cesar Higa Nomura ; Débora Fernandes Deus ; Elaine Rufo Tavares ; Fabiana Hanna Rached ; Fatima Rodrigues de Sousa e Freitas ; Gilbert Alexandre Sigal ; José Carlos Nicolau ; José Salvador Rodrigues de Oliveira ; leopoldo Alves Ribeiro Filho ; Luís Henrique Wolff Gowdak ; Maria Carolina Guido ; Noedir Antônio Groppo Stolf ; Nora Manoukian Forones ; Priscila Carvalho Melero da Silva ; Roger Chammas ; Silvia Regina Graziani ; Vital Paulino Costa
Associated scholarship(s):24/14347-7 - Treatment of Graft Vascular Disease with paclitaxel-loaded lipid nanoparticles: effects on inflammatory markers and plasma lipids, functional aspects of HDL, and serum MicroRNAs, BP.DR
24/06249-5 - Obtaining a new formulation of nanoparticles, LDE-melphalan: Synthesis of a lipophilic derivative of the chemotherapeutic agent, preparation of lipid nanoparticles and incorporation, stability, cytotoxicity and in vivo pharmacological tests., BP.PD
23/14558-5 - Technological improvement in the production of LDE nanoparticles carrying drugs: increase in production scale and technical training to maintain product quality., BP.TT

Abstract

In world pioneer studies, we showed nanoparticles (LDE) similar to the lipid structure of low-density lipoprotein (LDL) can concentrate anti-cancer agents, such as paclitaxel, etoposide, and methotrexate, in neoplastic and inflamed tissues. Using LDE as carrier, the toxicity of those agents was drastically reduced, whereas the pharmacologic actions were enhanced. The near-absence of toxicity leads us to use anti-cancer agents carried in LDE to treat non-oncologic diseases. We showed in animal models superior actions on atherosclerosis, acute myocardial infarction, heart transplantation, rheumatoid arthritis, and glaucoma. Recently, we showed the advantages of LDE-paclitaxel to treat women with ovarian carcinoma and of LDE-etoposide in conditioning chemotherapy for bone-marrow transplantation (BMT) in leukemia patients. This Project is aimed to develop new LDE-drug formulations, to deepen knowledge on the mechanisms of action of LDE as drug carrier, find new therapeutic targets, and to explore aspects of plasma lipoprotein metabolism using LDE as a tool. Chiefly, we aim to test LDE in the treatment of diseases of large prevalence in the general population, against which the current therapeutic tools are still in need of strong improvement regarding efficacy and tolerability. We intend to test LDE-paclitaxel treatment in patients with coronary and peripheral artery disease, patients with pancreatic cancer, and as adjuvant of glaucoma surgery. Moreover, we propose testing of LDE-methotrexate in head and neck cancer patients, with osteoarthrosis, rheumatoid arthritis. The use of LDE-etoposide in BMT for acute lymphoid leukemia is also proposed. Results are expected to convey a therapeutic revolution in different medical specialties by creating new approaches and higher standards of efficacy and tolerability in the treatment of several diseases and great socio-economic impact. (AU)

Articles published in Agência FAPESP Newsletter about the research grant:
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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)
CAMARGO, CRISTINA PIRES; GUIDO, MARIA CAROLINA; TAVARES, ELAINE RUFO; CARVALHO, PRISCILA OLIVEIRA; GEMPERLI, ROLF; MARANHAO, RAUL CAVALCANTE. Methotrexate-Loaded solid lipid nanoparticles enhance the viability of cutaneous flaps: potential for surgical wound healing. Journal of Drug Targeting, v. N/A, p. 9-pg., . (20/16215-0)

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