Inhalation of dimethyl fumarate-encapsulated sold lipid nanoparticles attenuate clinical signs of experimental autoimmune encephalomyelitis and pulmonary inflammatory dysfunction in mice

被引：10

作者：

Pinto, Barbara Fernandes ^{[1
]}

Brito Ribeiro, Lorena Natasha ^{[1
]}

Rolfsen Ferreira da Silva, Gisela Bevilacqua ^{[2
,3
]}

Freitas, Camila Simoes ^{[4
]}

Kraemer, Lucas ^{[4
,5
]}

Silva Oliveira, Fabricio Marcus ^{[5
]}

Climaco, Marianna Carvalho ^{[5
]}

Goncalves Mourao, Flavio Afonso ^{[1
,6
]}

Pinheiro Dos Santos, Gabryella Soares ^{[7
]}

Bela, Samantha Ribeiro ^{[7
]}

da Silva Gurgel, Isabella Luisa ^{[8
]}

Leite, Fabio de Lima ^{[2
]}

de Oliveira, Anselmo Gomes ^{[3
]}

Silva da Pascoa Vilela, Maura Regina ^{[1
]}

Oliveira-Lima, Onesia Cristina ^{[9
]}

Soriani, Frederico Marianetti ^{[8
]}

Fujiwara, Ricardo Toshio ^{[5
]}

Birbrair, Alexander ^{[7
]}

Russo, Remo Castro ^{[4
]}

Carvalho-Tavares, Juliana ^{[1
]}

机构：

[1] Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Physiol & Biophys, Neurosci Grp, Belo Horizonte, MG, Brazil

[2] Fed Univ Sao Carlos UFSCAR, Dept Phys Chem & Math, Nanoneurobiophys Res Grp, Sorocaba, SP, Brazil

[3] State Sao Paulo Univ UNESP, Sch Pharmaceut Sci, Drugs & Med Dept, Araraquara, SP, Brazil

[4] Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Physiol & Biophys, Lab Pulm Immunol & Mech, Belo Horizonte, MG, Brazil

[5] Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Physiol & Biophys, Lab Immunol & Genom Parasites, Belo Horizonte, MG, Brazil

[6] Fed Univ Minas Gerais UFMG, Ctr Technol & Res Magneto Resonance CTPMAG, Belo Horizonte, MG, Brazil

[7] Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Pathol, Belo Horizonte, MG, Brazil

[8] Fed Univ Minas Gerais UFMG, Inst Biol Sci, Dept Genet Ecol & Evolut, Lab Funct Genet, Belo Horizonte, MG, Brazil

[9] Fed Univ Goias UFG, Inst Biol Sci, Dept Pharmacol, Goiania, Go, Brazil

来源：

CLINICAL SCIENCE | 2022年 / 136卷 / 01期

基金：

巴西圣保罗研究基金会;

关键词：

BLOOD-BRAIN-BARRIER; PLACEBO-CONTROLLED PHASE-3; SOLUBLE-ANTIGEN ARRAYS; MULTIPLE-SCLEROSIS; ACID ESTERS; SPINAL-CORD; INTRANASAL DELIVERY; MOUSE MODEL; ORAL BG-12; T-CELLS;

D O I：

10.1042/CS20210792

中图分类号：

R-3 [医学研究方法]; R3 [基础医学];

学科分类号：

1001 ;

摘要：

Rationale: The FDA-approved Dimethyl Fumarate (DMF) as an oral drug for Multiple Sclerosis (MS) treatment based on its immunomodulatory activities. However, it also caused severe adverse effects mainly related to the gastrointestinal system. Objective: Investigated the potential effects of solid lipid nanoparticles (SLNs) containing DMF, administered by inhalation on the clinical signs, central nervous system (CNS) inflammatory response, and lung function changes in mice with experimental autoimmune encephalomyelitis (EAE). Materials and methods: EAE was induced using MOG(35-55) peptide in female C576116J mice and the mice were treated via inhalation with DMF-encapsulated SLN (CTRUSLN/DMF and EAE/SLN/DMF), empty SLN (CTRUSLN and EAE/SLN), or saline solution (CTRUsaline and EAE/saline), every 72 h during 21 days. Results: After 21 days post-induction, EAE mice treated with DMF-loaded SLN, when compared with EAE/saline and EAE/SLN, showed decreased clinical score and weight loss, reduction in brain and spinal cord injury and inflammation, also related to the increased influx of Foxp3(+) cells into the spinal cord and lung tissues. Moreover, our data revealed that EAE mice showed signs of respiratory disease, marked by increased vascular permeability, leukocyte influx, production of TNF-alpha and IL-17, perivascular and peribronchial inflammation, with pulmonary mechanical dysfunction associated with loss of respiratory volumes and elasticity, which DMF-encapsulated reverted in SLN nebulization. Conclusion: Our study suggests that inhalation of DMF-encapsulated SLN is an effective therapeutic protocol that reduces not only the CNS inflammatory process and disability progression, characteristic of EAE disease, but also protects mice from lung inflammation and pulmonary dysfunction.

引用

页码：81 / 101

页数：21