Abstract
BackgroundsDespite the advances of rheumatoid arthritis (RA) therapeutics, several patients do not receive adequate treatment due to the toxicity and/or insufficient response of drugs. The aim of this study is to design photothermally controlled drug release from multifunctional nanoparticles (MNPs) at a near-infrared (NIR) irradiated site to improve therapeutic efficacy for RA and reduce side effects.MethodsAu film was deposited onto methotrexate (MTX)-loaded poly(ethylene glycol)-poly(lactic-co-glycolic acid) (PLGA) nanoparticles, resulting in MTX-loaded MNPs. The synergistic effects of MTX-loaded MNPs with NIR irradiation were investigated using RA fibroblast-like synoviocytes (FLSs) and collagen-induced arthritis (CIA) mice.ResultsUpon NIR irradiation, NIR resonance of the Au half-shell generated heat locally, accelerating MTX release from PLGA nanoparticles. In vivo NIR images of MTX-loaded MNPs indicated effective delivery of the MNPs to the inflamed joints. Moreover, in collagen-induced arthritis mice, MTX-loaded MNPs containing 1/1400 of MTX solution (repeated-dose administration) had therapeutic effects comparable to conventional treatment with MTX solution. In vitro experiments showed higher therapeutic efficacy of MTX-loaded MNPs with NIR irradiation than that of chemotherapy alone.ConclusionsA combination therapy of MTX-loaded MNP and NIR irradiation showed durable and good treatment efficacy for the suppression of arthritis in a single administration of small dose of MTX. Our results demonstrate that the treatment modality using drug-loaded MNP with NIR irradiation may be a promising therapeutic strategy for the treatment of RA and allow in vivo NIR optical imaging.
Highlights
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and bony erosion, leading to bone destruction and disability [1]
Ex vivo NIR imaging MTX-loaded Multifunctional nanoparticle (MNP) (200 μl, 1 mg/ml dispersed in Phosphatebuffered saline (PBS)) were injected intravenously into the collagen-induced arthritis (CIA) mice
Compared to the inflamed paw unexposed to NIR, the inflamed paw exposed to NIR yielded a higher intensity of rhodamine at 1 and 24 h due to an enhanced release rate of rhodamine caused by NIR irradiation
Summary
Rheumatoid arthritis (RA) is a chronic inflammatory disease characterized by synovial hyperplasia and bony erosion, leading to bone destruction and disability [1]. The mainstay of RA treatment is the administration of disease-modifying anti-rheumatic drugs (DMARDs) aimed at improving inflammation and retarding disease progression [2]. MTX has been widely used as a DMARD and exhibits excellent efficacy and an acceptable toxicity profile [3, 4]. Approximately 30% of RA patients cannot tolerate MTX because of its side effects, which include nausea, vomiting, stomatitis, hepatotoxicity, and bone marrow suppression [5]. The adverse effects of MTX are dose-dependent, so several delivery systems using nanoparticles (NPs), liposomes, microspheres, and different polymers have been suggested to improve the delivery of MTX [6]
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