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Development of solid lipid nanoparticles containing dimethyl fumarate intranasal for multiple sclerosis

Grant number: 13/22141-5
Support Opportunities:Scholarships in Brazil - Post-Doctoral
Effective date (Start): March 01, 2014
Effective date (End): February 28, 2018
Field of knowledge:Health Sciences - Pharmacy - Pharmaceutical Technology
Principal Investigator:Fabio de Lima Leite
Grantee:Gisela Bevilacqua Rolfsen Ferreira da Silva
Host Institution: Centro de Ciências e Tecnologias para a Sustentabilidade (CCTS). Universidade Federal de São Carlos (UFSCAR). Sorocaba , SP, Brazil
Associated scholarship(s):16/14264-8 - Comparative study of the clinical efficiency of dimethyl fumarate in gelatin capsules and dimethyl fumarate in solid lipid nanoparticles administered by the oral and subcutaneous routes, respectively, BE.EP.PD


Multiple sclerosis (MS) is a chronic inflammatory autoimmune disease that causes neuroinflammation and CNS demyelination . The dimethyl fumarate (DMF) is a lipophilic drug forty years ago used to treat psoriasis. Recent studies show that oral administration of DMF is able to reduce the relapse of MS patients and reduce the formation of new lesions in the white matter through immunomodulatory effects through activation of the transcription factor Nrf2. However, the clinical utility of DMF can be impaired by poor retention in the CNS and transport to the complexity of the blood brain barrier. For this reason, there is a need for delivery systems to selectively reach the brain. The solid lipid nanoparticles ( SLN ) can meet this objective, carrying drugs poorly soluble in water. The intranasal route (IN) is considered an alternative which can allow the effect of the CNS drug more efficiently because the drug to pass beyond the barrier, is not subject to first-pass hepatic metabolism. Due to the activity of DMF in MS and its low solubility in water, there is a need for a nanostructured carrier system capable of overcoming the blood brain barrier and direct it to the CNS . Thus, we can obtain better therapeutic efficacy with minimized side effects and reducing the frequency of drug administration. The main objective of this work is to develop the NLS containing DMF and characterize them physicochemically. Furthermore, it should be quantify the encapsulation efficiency, the in vitro release of the drug, the permeation of the nasal mucosa and to evaluate the activity of DMF in cultured oligodendrocytes. (AU)

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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)
PINTO, BARBARA FERNANDES; BRITO RIBEIRO, LORENA NATASHA; ROLFSEN FERREIRA DA SILVA, GISELA BEVILACQUA; FREITAS, CAMILA SIMOES; KRAEMER, LUCAS; SILVA OLIVEIRA, FABRICIO MARCUS; CLIMACO, MARIANNA CARVALHO; GONCALVES MOURAO, FLAVIO AFONSO; PINHEIRO DOS SANTOS, GABRYELLA SOARES; BELA, SAMANTHA RIBEIRO; et al. nhalation of dimethyl fumarate-encapsulated sold lipid nanoparticles attenuate clinical signs of experimental autoimmune encephalomyelitis and pulmonary inflammatory dysfunction in mic. Clinical Science, v. 136, n. 1, p. 81-101, . (16/14264-8, 13/22141-5)
DA SILVA, GISELA BEVILACQUA ROLFSEN FERREIRA; DAS NEVES, SOFIA PEREIRA; OLIVEIRA, SUSANA CRISTINA ROQUE; MARQUES, FERNANDA; DE OLIVEIRA, ANSELMO GOMES; LEITE, FABIO DE LIMA; CERQUEIRA, JOAO JOSE. Comparative effectiveness of preventive treatment with dimethyl fumarate-loaded solid lipid nanoparticles and oral dimethyl fumarate in a mouse model of multiple sclerosis. Journal of Autoimmunity, v. 132, p. 8-pg., . (13/22141-5, 16/14264-8)

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