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 Opportunities: Research Projects - Thematic Grants
• Start date: November 01, 2018
• End date: October 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - Biochemical and Molecular Pharmacology
• Principal Investigator: Marcelo Henrique Napimoga
• Grantee: Marcelo Henrique Napimoga
• Host 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
• Pesquisadores principais: Juliana Trindade Clemente Napimoga
• Associated researchers: Cristina Gomes de Macedo Maganin ; Daniele Ribeiro de Araujo ; Leonardo Fernandes Fraceto ; Nathalie Ferreira Silva de Melo ; Waldiceu Aparecido Verri Junior
• Associated research grant(s): 23/03596-3 - 2023 IADR/LAR General Session & Exhibition with WCPD, AR.EXT
• 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)

Scientific publications

(14)

(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)

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. (17/22334-9)

TEIXEIRA, JULIANA M.; PIMENTEL, RAFAEL M.; ABDALLA, HENRIQUE B.; DE SOUSA, HORTENCIA M. X.; MACEDO, CRISTINA G.; NAPIMOGA, MARCELO H.; TAMBELI, CLAUDIA H.; OLIVEIRA-FUSARO, MARIA C. G.; CLEMENTE-NAPIMOGA, JULIANA T.. P2X7-induced nociception in the temporomandibular joint of rats depends on inflammatory mechanisms and C-fibres sensitization. EUROPEAN JOURNAL OF PAIN, v. 25, n. 5, FEB 2021. (17/22334-9)

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, p. 9-pg., 2019-09-01. (17/22334-9)

BASTING, ROSANNA TARKANY; NAPIMOGA, MARCELO HENRIQUE; SILVA, CARLOS ANTOONIO TRINDADE; ABDALLA, HENRIQUE BALLASSINI; DURSO, BRAZ CAMPOS; MARTINS, LEOPOLDO HENRIQUE BARBOZA; CAVALCANTI, HERBERT DE ABREU; HAMMOCK, BRUCE D.; CLEMENTE-NAPIMOGA, JULIANA TRINDADE. Soluble epoxide hydrolase inhibitor blockage microglial cell activation in subnucleus caudalis in a persistent model of arthritis. International Immunopharmacology, v. 120, p. 15-pg., 2023-05-23. (17/22334-9, 19/04276-7)

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. (13/09524-2, 17/22334-9)

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. (17/22334-9)

ABDALLA, HENRIQUE B.; ALVAREZ, CARLA; WU, YU-CHIAO; ROJAS, PAOLA; HAMMOCK, BRUCE D.; MADDIPATI, KRISHNA R.; TRINDADE-DA-SILVA, CARLOS ANTONIO; SOARES, MARIANA Q. S.; CLEMENTE-NAPIMOGA, JULIANA T.; KANTARCI, ALPDOGAN; et al. Soluble epoxide hydrolase inhibition enhances production of specialized pro-resolving lipid mediator and promotes macrophage plasticity. British Journal of Pharmacology, v. N/A, p. 19-pg., 2023-01-30. (17/22334-9, 19/22645-0)

ABDALLA, H. B.; NAPIMOGA, M. H.; TRINDADE-DA-SILVA, C. A.; GUIMARAES, M.; LOPES, M.; DOS SANTOS, V, P. C.; SILVA, W. A. BUARQUE E.; SILVA, F. ANDRADE E.; CLEMENTE-NAPIMOGA, J. T.. Occlusal Trauma Induces Neuroimmune Crosstalk for a Pain State. JOURNAL OF DENTAL RESEARCH, OCT 2021. (19/04276-7, 17/22334-9)

BASTING, ROSANNA TARKANY; NAPIMOGA, MARCELO HENRIQUE; DE LIMA, JULIANA MOREIRA; DE FREITAS, NADIR SEVERINA; CLEMENTE-NAPIMOGA, JULIANA TRINDADE. Fast and accurate protocol for histology and immunohistochemistry reactions in temporomandibular joint of rats. ARCHIVES OF ORAL BIOLOGY, v. 126, JUN 2021. (17/22334-9)

TRINDADE DA SILVA, CARLOS ANTONIO; CLEMENTE-NAPIMOGA, JULIANA TRINDADE; ABDALLA, HENRIQUE BALLASSINI; BASTING, ROSANNA TARKANY; HENRIQUE NAPIMOGA, SOLELY MARCELO. Peroxisome proliferator-activated receptor-gamma (PPAR gamma) and its immunomodulation function: current understanding and future therapeutic implications. EXPERT REVIEW OF CLINICAL PHARMACOLOGY, v. 15, n. 3, p. 9-pg., 2022-05-02. (19/01151-9, 17/22334-9, 19/04276-7)

ABDALLA, HENRIQUE BALLASSINI; NAPIMOGA, MARCELO HENRIQUE; TEIXEIRA, JULIANA MAIA; TRINDADE-DA-SILVA, CARLOS ANTONIO; PIERONI, VICTOR LUIS; DOS SANTOS ARAUJO, FERNANDA SOUTO MAIOR; HAMMOCK, BRUCE D.; CLEMENTE-NAPIMOGA, JULIANA TRINDADE. Soluble epoxide hydrolase inhibition avoid formalin-induced inflammatory hyperalgesia in the temporomandibular joint. INFLAMMOPHARMACOLOGY, v. 30, n. 3, p. 10-pg., 2022-03-18. (18/05575-5, 17/22334-9)

ETTLIN, DOMINIK A.; NAPIMOGA, MARCELO HENRIQUE; MEIRA E CRUZ, MIGUEL; CLEMENTE-NAPIMOGA, JULIANA TRINDADE. Orofacial musculoskeletal pain: An evidence-based bio-psycho-social matrix model. NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS, v. 128, p. 12-20, SEP 2021. (17/22334-9)

PEREIRA, ELIANA DE SOUZA BASTOS MAZUQUELI; BASTING, ROSANNA TARKANY; ABDALLA, HENRIQUE BALLASSINI; GARCEZ, AGUINALDO SILVA; NAPIMOGA, MARCELO HENRIQUE; CLEMENTE-NAPIMOGA, JULIANA TRINDADE. Photobiomodulation inhibits inflammation in the temporomandibular joint of rats. JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY B-BIOLOGY, v. 222, SEP 2021. (17/22334-9)

CLEMENTE-NAPIMOGA, JULIANA TRINDADE; MENDES, VAGNER; TRINDADE-DA-SILVA, CARLOS ANTONIO; DE CARVALHO, GUSTAVO; PARANHOS, ALETHEIA CALDEIRA GONCALVES ALCANTARA; SILVA, FREDERICO ANDRADE E; SILVA, WILKENS AURELIO BUARQUE E; NAPIMOGA, MARCELO HENRIQUE; ABDALLA, HENRIQUE BALLASSINI. Experimental traumatic occlusion drives immune changes in trigeminal ganglion. International Immunopharmacology, v. 122, p. 9-pg., 2023-09-01. (17/22334-9, 19/04276-7)