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Use of drug delivery systems for the development and application of anti-inflammatory agents with potential immunomodulatory and neuroprotective effects

Grant number: 17/22334-9
Support type:Research Projects - Thematic Grants
Duration: November 01, 2018 - October 31, 2023
Field of knowledge:Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
Principal Investigator:Marcelo Henrique Napimoga
Grantee:Marcelo Henrique Napimoga
Home Institution: Centro de Pesquisas Odontológicas São Leopoldo Mandic. Faculdade São Leopoldo Mandic (SLMANDIC). Sociedade Regional de Ensino e Saúde S/S Ltda (SRES). Campinas , SP, Brazil
Co-Principal Investigators:Juliana Trindade Clemente Napimoga
Assoc. researchers:Cristina Gomes de Macedo Maganin ; Daniele Ribeiro de Araujo ; Leonardo Fernandes Fraceto ; Nathalie Ferreira Silva de Melo ; Waldiceu Aparecido Verri Junior
Associated scholarship(s):19/01151-9 - Evaluation of the immunomodulatory and neuroprotective effect of the epoxy hydrolase inhibitor, TPPU, on persistent inflammatory hypernociception induced by arthritis in the temporomandibular joint of rats., BP.PD
19/04276-7 - The use of micro-needles coated with drugs for the control of pain and inflammation, BP.PD

Abstract

This project proposes the use of two drug release systems, the polymer nanoparticles and the microneedles patch, for the development and applicability of two formulations with immunomodulatory and neuroprotective potential. Epoxy-eicosatrienoic acid (EET) is a product of arachidonic acid metabolism catalyzed by cytochrome P450 epoxygenases. These small molecules are lipid mediators, which have been shown to be a new therapeutic strategy for inflammatory pathologies. The development of metabolically stable inhibitors of sEH, such as TPPU (1-trifluoromethoxyphenyl-3- (1-propionylpiperidin-4-yl)), which was developed and patented by Dr. Bruce Hammock (international collaborator of this project), remain EET levels elevated in tissues for a long time by mediating important resolving actions of the inflammatory cascade. The first phase of this project proposes to investigate the immunomodulatory and neuroprotective potential of TPPU in degenerative arthritic conditions, as well as the neurochemical mechanisms involved in this process. The second phase of this project proposes the development of a nanostructured formulation containing TPPU to enhance the therapeutic properties of TPPU and to enable its release more efficiently in the target tissues. In order to search for more effective and less invasive methods for the application of drugs to modulate inflammatory pain conditions, the last phase of this project will be to evaluate whether the use of a patch with drug-coated microneedles developed by Dr. Harvinder S. Gill (international collaborator of this project), has a real clinical applicability for the control of inflammation and joint pain, specifically Temporomandibular Joint (TMJ). Patients with temporomandibular dysfunction will be treated with microneedles coated with tramadol, considering recent data that demonstrated its potent anti-inflammatory effect when applied directly to the periarticular tissues. The development of this clinical study aims to establish a new clinical strategy for the control of inflammatory pain, in a less invasive and more effective way, for inflammatory joint conditions. In summary, this project seeks the development of products with technological innovation with real clinical feasibility. As future perspectives, based on the experimental results obtained, the potential association of microneedles coated with a nanostructured formulation of TPPU, a new patentable product, is envisaged; and considering the fact that sEH inhibitors have already been tested in 5 different animal orders, the planning of preclinical and clinical trials of TPU-coated microneedle as a next step. (AU)

Articles published in other media outlets (48 total):
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Jornal de Piracicaba: Molécula criada em laboratório apresenta resultados positivos (26/Jul/2020)
SBT Interior: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (23/Jul/2020)
UOL: Molécula criada em laboratório auxilia no tratamento da artrite (22/Jul/2020)
proZesa (Espanha): Molécula muestra resultados positivos en el tratamiento de la artritis (31/Aug/2020)
iNGENET Bitácora (México): Una molécula creada en laboratorio muestra resultados positivos en el tratamiento de la artritis (29/Aug/2020)
Al Día (Cuba): Una molécula creada en laboratorio muestra resultados positivos en el tratamiento de la artritis (25/Aug/2020)
El Diario del Centro del País (Argentina) online: Una molécula muestra resultados positivos para tratar la artritis (25/Aug/2020)
ID - Investigación y Desarrollo (México) online: Una molécula creada en laboratorio muestra resultados positivos en el tratamiento de la artritis (24/Aug/2020)
Vanguardia (México): Una molécula creada en laboratorio muestra resultados positivos en el tratamiento de la artritis (24/Aug/2020)
Santé blog (França): Arthrite: La nouvelle molécule qui inhibe l’érosion (24/Aug/2020)
Maestroviejo (Espanha): Una molécula creada en laboratorio muestra resultados positivos en el tratamiento de la artritis (23/Aug/2020)
NCYT Amazings (Espanha): Una molécula creada en laboratorio muestra resultados positivos en el tratamiento de la artritis (22/Aug/2020)
El Mundo al Instante (EUA): Molécula creada en un laboratorio muestra resultados positivos en el tratamiento de la artritis (22/Aug/2020)
M3 India (Índia): Lab-created molecule achieves positive results in the treatment of arthritis (14/Aug/2020)
Programa InfoSalud (Argentina): Una molécula creada en laboratorio muestra resultados positivos en el tratamiento de la artritis (13/Aug/2020)
News Medical (Austrália): New molecule shows potential therapeutic effects against arthritis (12/Aug/2020)
Brinkwire (Reino Unido): Lab-created molecule achieves positive results in the treatment of arthritis. (12/Aug/2020)
Drug Target Review (Reino Unido): Novel molecule effectively treats arthritis in mice, study shows (12/Aug/2020)
Mindzilla (Reino Unido): Lab-created molecule achieves positive results in the treatment of arthritis. (12/Aug/2020)
Hekim.pro Professional Doctors (Azerbaijão): Lab-created molecule achieves positive results in the treatment of arthritis. (12/Aug/2020)
AZo Life Sciences: Novel molecule shown to have potential therapeutic effects for arthritis (12/Aug/2020)
Knowledia (França): New molecule shows potential therapeutic effects against arthritis (12/Aug/2020)
Medical Xpress (Reino Unido): Lab-created molecule achieves positive results in the treatment of arthritis (11/Aug/2020)
Science Codex: Lab-created molecule achieves positive results in the treatment of arthritis (11/Aug/2020)
Scienmag Science Magazine (Reino Unido): Lab-created molecule achieves positive results in the treatment of arthritis (11/Aug/2020)
Brightsurf: Lab-created molecule achieves positive results in the treatment of arthritis (11/Aug/2020)
CBS7 (EUA): New Molecule Suppresses Inflammatory Process in Mice With Genetically-Induced Arthritis (11/Aug/2020)
KingfirthHealthandFitness: Lab-created molecule achieves positive results in the treatment of arthritis (11/Aug/2020)
France 24 (França): Lab-created molecule achieves positive results in the treatment of arthritis. (11/Aug/2020)
Home Health Choices: Lab-created molecule achieves constructive ends in the remedy of arthritis (11/Aug/2020)
Erwotex.net: Lab-created molecule achieves positive results in the treatment of arthritis (11/Aug/2020)
Jornal Dia Dia: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (27/Jul/2020)
Saber Atualizado: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (26/Jul/2020)
Região Noroeste : Molécula apresenta resultados positivos no tratamento da artrite (24/Jul/2020)
Jornal Folha da Terra (Itupeva, SP) online: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (24/Jul/2020)
Noticias Noroeste online: Molécula apresenta resultados positivos no tratamento da artrite (24/Jul/2020)
Programa InfoSalud (Argentina): Una molécula creada en laboratorio presenta resultados positivos en el tratamiento de la artritis (24/Jul/2020)
Portal do Governo do Estado de São Paulo: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (23/Jul/2020)
Notícias de Campinas: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (23/Jul/2020)
Mix Vale: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (23/Jul/2020)
Portal da Enfermagem: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (23/Jul/2020)
Mundo e Meio: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (23/Jul/2020)
Plantão News (MT): Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (22/Jul/2020)
Planeta online: Molécula criada em laboratório obtém resultados positivos contra artrite (22/Jul/2020)
Blog Jornal da Mulher: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (22/Jul/2020)
Atemporal: Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (22/Jul/2020)
Lúpuslesles: FAPESP - Molécula criada em laboratório apresenta resultados positivos no tratamento da artrite (22/Jul/2020)
Jornal Fatos & Notícias: Molécula criada em laboratório obtém resultados positivos contra artrite (22/Jul/2020)

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)
NAPIMOGA, MARCELO HENRIQUE; DANTAS FORMIGA, WESLLEY DANNY; ABDALLA, HENRIQUE BALLASSINI; TRINDADE-DA-SILVA, CARLOS ANTONIO; VENTURIN, CAMILA MOTTA; MARTINEZ, ELIZABETH FERREIRA; ROSSANEIS, ANA CAROLINA; VERRI JR, WALDICEU A.; CLEMENTE-NAPIMOGA, JULIANA TRINDADE. Secreted Osteoclastogenic Factor of Activated T Cells (SOFAT) Is Associated With Rheumatoid Arthritis and Joint Pain: Initial Evidences of a New Pathway. FRONTIERS IN IMMUNOLOGY, v. 11, JUL 28 2020. Web of Science Citations: 0.
TRINDADE-DA-SILVA, CARLOS A.; CLEMENTE-NAPIMOGA, JULIANA T.; ABDALLA, HENRIQUE B.; ROSA, SERGIO MARCOLINO; UEIRA-VIEIRA, CARLOS; MORISSEAU, CHRISTOPHE; VERRI JR, WALDICEU A.; MARTINS MONTALLI, VICTOR ANGELO; HAMMOCK, BRUCE D.; NAPIMOGA, MARCELO H. Soluble epoxide hydrolase inhibitor, TPPU, increases regulatory T cells pathway in an arthritis model. FASEB JOURNAL, v. 34, n. 7 MAY 2020. Web of Science Citations: 0.
ABDALLA, HENRIQUE BALLASSINI; JAIN, AMIT K.; NAPIMOGA, MARCELO HENRIQUE; CLEMENTE-NAPIMOGA, JULIANA TRINDADE; GILL, HARVINDER SINGH. Microneedles Coated with Tramadol Exhibit Antinociceptive Effect in a Rat Model of Temporomandibular Hypernociception. Journal of Pharmacology and Experimental Therapeutics, v. 370, n. 3, SI, p. 834-842, SEP 1 2019. Web of Science Citations: 1.

Please report errors in scientific publications list by writing to: cdi@fapesp.br.