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Construction of a Nano-Controlled Release Methotrexate Delivery System for the Treatment of Rheumatoid Arthritis by Local Percutaneous Administration.

ABSTRACT: A drug delivery system was specifically designed for the treatment of rheumatoid arthritis (RA) by local percutaneous administration and the nano-controlled release of methotrexate (MTX). The release behavior of MTX from the synthesized MTX-mSiO₂@PDA system was investigated in vitro and in vivo. The obtained results show that after 48 h, twice as much MTX (cumulative amount) is released at pH 5.5 than at pH 7.4. This suggests that the MTX-mSiO₂@PDA system exhibits a good pH sensitivity. In vitro local percutaneous administration experiments revealed that the cumulative amount of MTX transferred from MTX-mSiO₂@PDA to pH 5.0 receptor fluid through the whole skin was approximately three times greater than the amount transferred to pH 7.4 receptor fluid after 24 h. Moreover, in vivo experiments conducted on a complete induced arthritis (CIA) model in DBA/1 mice demonstrated that the thickness of a mouse's toes decreases to nearly 65% of the initial level after 27 days of local percutaneous MTX-mSiO₂@PDA administration. Compared to the mice directly injected with MTX, those administered with MTX-mSiO₂@PDA by local percutaneous application exhibit much lower toe thickness deviation, which indicates that the latter group experiences a better cure stability. Overall, these results demonstrate that the local percutaneous administration of MTX delivery systems characterized by nano-controlled release may play an important role in RA therapy.

SUBMITTER: Guo T

PROVIDER: S-EPMC8624172 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:IntroductionLimited data are available to explain nonadherence to methotrexate (MTX) therapy in patients with rheumatoid arthritis (RA). Better understanding of patterns of MTX use and reasons for nonadherence may help identify patients who would benefit from alternative RA treatments and potentially aid in developing strategies to increase overall adherence. The purpose of this study was to assess patients' self-reported adherence to MTX and to identify reasons for nonadherence.MethodsPatient panel members in the US self-reporting a diagnosis of RA of ?3 months' and current MTX use of ?4 weeks' duration, with or without concomitant use of another RA prescription medication, participated in this cross-sectional, web-based survey.ResultsThe sample population (251 MTX monotherapy, 250 MTX combination therapy) was predominantly female, white, non-Hispanic, and educated; 48% were 18-44 years-old, 47% had medical comorbidities, 66% were first diagnosed with RA ?5 years earlier, 51% reported MTX use of <1 year, and 83% reported oral MTX use. Forty-two percent reported not taking MTX exactly as prescribed. Reasons for nonadherence included forgetting to take it (33%), not needing it when feeling well (24%), and concern about long-term safety (24%). Among nonadherent patients, 53% took smaller doses, 52% skipped doses, and 6% reported other nonprescribed ways of taking MTX. Younger age, male sex, and shorter duration of MTX use were associated with poorer self-reported adherence. Compared with monotherapy patients, combination therapy patients, particularly those taking ?2 other RA prescriptions, were less likely to report high adherence.ConclusionNearly half the sample reported poor MTX adherence because they forgot to take it, thought it was not needed when they felt well, or had long-term safety concerns. Patients taking ?2 other RA prescription medications were less likely to report good adherence. Reducing treatment burden without sacrificing efficacy may be a strategy worth evaluating.

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Construction of a Nano-Controlled Release Methotrexate Delivery System for the Treatment of Rheumatoid Arthritis by Local Percutaneous Administration.

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