Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis
| Autor: | Marcos Luciano Bruschi, Aline Martins dos Santos, Giovane Galdino, Flávia Chiva Carvalho, Sandra Barbosa Neder Agostini, Jennifer Tavares Jacon Freitas, Rômulo Dias Novaes, Merelym Ketterym de Oliveira, Denismar Alves Nogueira, Jéssica Bassi da Silva, Rafaela Figueiredo Rodrigues, Lívia Maria Silvestre Elisei, Luana Aparecida dos Reis Giusto, Rafaela Silva dos Santos, Mônica Esselin de Sousa Lino, Iago Henrique Silva Malta, Thamyris Reis Moraes, Gislaine Ribeiro Pereira |
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| Přispěvatelé: | Universidade Federal de Alfenas, Universidade Estadual de Maringá (UEM), Universidade Estadual Paulista (Unesp) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
musculoskeletal diseases
Drug Chitooligosaccharide media_common.quotation_subject Drug delivery system Pharmaceutical Science Arthritis 02 engineering and technology Pharmacology 030226 pharmacology & pharmacy Arthritis Rheumatoid 03 medical and health sciences 0302 clinical medicine immune system diseases In vivo medicine Animals heterocyclic compounds Rheumatoid arthritis skin and connective tissue diseases media_common Chitosan Hypromellose phthalate Chemistry Hydrogels Poloxamer 021001 nanoscience & nanotechnology medicine.disease Polyelectrolytes Rats Polyelectrolyte complexes Drug Liberation Methotrexate Drug delivery Self-healing hydrogels 0210 nano-technology medicine.drug |
| Zdroj: | Scopus Repositório Institucional da UNESP Universidade Estadual Paulista (UNESP) instacron:UNESP |
| Popis: | Made available in DSpace on 2021-06-25T10:32:23Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-08-01 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. Escola de Farmácia Departamento de Fármacos e Alimentos Universidade Federal de Alfenas Instituto de Ciência da Motricidade Universidade Federal de Alfenas Instituto de Química Universidade Federal de Alfenas Instituto de Ciências Biomédicas Departamento de Ciências Fisiológicas Universidade Federal de Alfenas Laboratório de Pesquisa e Desenvolvimento de Sistemas de Liberação de Fármacos Departamento de Farmácia Universidade Estadual de Maringá Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Julio de Mesquita Filho”. UNESP Instituto de Ciências Exatas Universidade Federal de Alfenas Instituto de Ciências Biomédicas Departamento de Biologia Estrutural Universidade Federal de Alfenas Faculdade de Ciências Farmacêuticas Universidade Estadual Paulista “Julio de Mesquita Filho”. UNESP |
| Databáze: | OpenAIRE |
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