Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis

被引：10
|
作者：
Neder Agostini, Sandra Barbosa [1 ]
Silva Malta, Iago Henrique [2 ]
Rodrigues, Rafaela Figueiredo [1 ]
Jacon Freitas, Jennifer Tavares [1 ]
de Sousa Lino, Monica Esselin [1 ]
dos Santos, Rafaela Silva [2 ]
Elisei, Livia Silvestre [2 ]
Moraes, Thamyris Reis [2 ]
dos Reis Giusto, Luana Aparecida [3 ]
Ketterym de Oliveira, Merelym [4 ]
da Silva, Jessica Bassi [5 ]
Bruschi, Marcos Luciano [5 ]
dos Santos, Aline Martins [6 ]
Nogueira, Denismar Alves [7 ]
Novaes, Romulo Dias [8 ]
Pereira, Gislaine Ribeiro [1 ]
Galdino, Giovane [2 ]
Carvalho, Flavia Chiva [1 ]
机构：
[1] Univ Fed Alfenas, Dept Farm & Alimentos, Escola Farm, Alfenas, MG, Brazil
[2] Univ Fed Alfenas, Inst Ciencia Motricidade, Alfenas, MG, Brazil
[3] Univ Fed Alfenas, Inst Quim, Alfenas, MG, Brazil
[4] Univ Fed Alfenas, Inst Ciencias Biomed, Dept Ciencias Fisiol, Alfenas, MG, Brazil
[5] Univ Estadual Maringa, Dept Farm, Lab Pesquisa & Desenvolvimento Sistemas Liberacao, Maringa, Parana, Brazil
[6] Univ Estadual Paulista, UNESP, Fac Ciencias Farmaceut, Araraquara, SP, Brazil
[7] Univ Fed Alfenas, Inst Ciencias Exatas, Alfenas, MG, Brazil
[8] Univ Fed Alfenas, Inst Ciencias Biomed, Dept Biol Estrutural, Alfenas, MG, Brazil
来源：
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES | 2021年 / 163卷
关键词：
Rheumatoid arthritis; Chitosan; Chitooligosaccharide; Hypromellose phthalate; Methotrexate; Polyelectrolyte complexes; Drug delivery system; WATER-SOLUBLE CHITOSAN; DRUG-DELIVERY; IN-VITRO; MUCOADHESIVE PROPERTIES; INFLAMMATORY CYTOKINE; OLIGOSACCHARIDES; MICROSPHERES; CARTILAGE; JOINT; EFFICACY;
D O I：
10.1016/j.ejps.2021.105856
中图分类号：
R9 [药学];
学科分类号：
1007 ;
摘要：
This work proposes new methotrexate (MTX) loaded drug delivery systems (DDS) to treat rheumatoid arthritis via the intra-articular route: a poloxamer based thermosensitive hydrogel (MTX-HG), oligochitosan and hypromellose phthalate-based polyelectrolyte complexes (MTX-PEC) and their association (MTX-PEC-HG). MTX-PEC showed 470 +/- 166 nm particle size, 0.298 +/- 0.108 polydispersity index, +26 +/- 2 mV and 74.3 +/- 5.8% MTX efficiency entrapment and particle formation was confirmed by infrared spectroscopy and thermal analysis. MTX-HG and MTX-PEC-HG gelled at 36.7 degrees C. MTX drug release profile was prolonged for MTX-HG and MTX-PEC-HG, and faster for MTX-PEC and free MTX. The in vivo effect of the MTX-DDSs systems was evaluated in induced arthritis rats as single intra-articular dose. The assessed parameters were the mechanical nociceptive threshold, the plasmatic IL-1 beta level and histological analysis of the tibiofemoral joint. MTX-HG and MTX-PEC-HG performance were similar to free MTX and worse than oral MTX, used as positive control. All DDSs showed some irritative effect, for which further studies are required. MTX-PEC was the best treatment on recovering cartilage damage and decreasing allodynia. Thus, MTX-PEC demonstrated potential to treat rheumatoid arthritis, with the possibility of decreasing the systemic exposure to the drug.
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页数：15
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