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

• Autor(a) principal: Agostini, Sandra Barbosa Neder
• Data de Publicação: 2021
• Outros Autores: Malta, Iago Henrique Silva, Rodrigues, Rafaela Figueiredo, Freitas, Jennifer Tavares Jacon, Lino, Mônica Esselin de Sousa, dos Santos, Rafaela Silva, Elisei, Lívia Silvestre, Moraes, Thamyris Reis, Giusto, Luana Aparecida dos Reis, de Oliveira, Merelym Ketterym, Bassi da Silva, Jéssica, Bruschi, Marcos Luciano, Santos, Aline Martins dos [UNESP], Nogueira, Denismar Alves, Novaes, Rômulo Dias, Pereira, Gislaine Ribeiro, Galdino, Giovane, Carvalho, Flávia Chiva
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.ejps.2021.105856; http://hdl.handle.net/11449/206457
• topic: Chitooligosaccharide; Chitosan; Drug delivery system; Hypromellose phthalate; Methotrexate; Polyelectrolyte complexes; Rheumatoid arthritis

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°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-1β 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.