Preclinical evaluation of methotrexate-loaded polyelectrolyte complexes and thermosensitive hydrogels as treatment for rheumatoid arthritis
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Data
2021-08-01
Autores
Agostini, Sandra Barbosa Neder
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
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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.
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Chitooligosaccharide, Chitosan, Drug delivery system, Hypromellose phthalate, Methotrexate, Polyelectrolyte complexes, Rheumatoid arthritis
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European Journal of Pharmaceutical Sciences, v. 163.