High Efficacy Combined Microneedles Array with Methotrexate Nanocrystals for Effective Anti-Rheumatoid Arthritis

被引:17
|
作者
Wei, Fang [1 ]
Wang, Qiuyue [1 ]
Liu, Hang [1 ]
Yang, Xuejing [1 ]
Cao, Wenyu [1 ]
Zhao, Weiman [1 ]
Li, Yingying [1 ]
Zheng, Lijie [1 ]
Ma, Tao [1 ,2 ]
Wang, Qingqing [1 ,2 ,3 ]
机构
[1] Bengbu Med Coll, Sch Pharm, Bengbu 233030, Anhui, Peoples R China
[2] Bengbu Med Coll, Engn Res Ctr Biochem Pharmaceut Anhui Prov, Bengbu 233030, Anhui, Peoples R China
[3] Bengbu BBCA Med Sci Co Ltd, Bengbu 233030, Anhui, Peoples R China
来源
INTERNATIONAL JOURNAL OF NANOMEDICINE | 2022年 / 17卷
关键词
nanocrystals; inflammation; dissolving microneedles array; transdermal; rheumatoid arthritis; NANOSUSPENSIONS; THERAPY; UPDATE;
D O I
10.2147/IJN.S365523
中图分类号
TB3 [工程材料学];
学科分类号
0805 ; 080502 ;
摘要
Introduction: Methotrexate (MTX) is the first-line drug for the treatment of rheumatoid arthritis (RA) in several countries. However, MTX has an extremely low solubility in water, and the side effects caused by its delivery mode restrict its curative effect. In this study, we designed a dissolving microneedles array (DMNA) containing MTX nanocrystals (MTX-NCs) (MTX-NC@DMNA) to improve the treatment of RA. DMNA-based drug delivery combines the advantages of patient compliance with the use of transdermal drug delivery systems and high-efficiency injection administration; thus, it can mitigate the side effects that result from current administration routes. Carrier-free and surfactant-free MTX-NCs were prepared to overcome bioavailability limitations and poor drug loading problems. Methods: The MTX-NCs prepared by reverse solvent precipitation method was encapsulated in the DMNA. The morphology, mechanical properties, safety, stability and in vivo dissolution were evaluated, and its pharmacodynamic characteristics were assessed in a rat model of RA. Results: The particle size of the MTX-NCs was 148.1 +/- 10.1 nm. The MTX-NC@DMNA were found to be rigid enough to penetrate the skin and deliver the drug successfully. The results indicated effective skin recovery after removal of the DMNA. It was found that the MTX-NC@DMNA significantly reduced foot swelling in the rats and regulated the balance in the levels of related cytokines. It also reduced pathological damage to the synovium, joint, and cartilage, and effectively alleviated organ injury in the rats. Conclusion: Transdermal administration of MTX-NC@DMNA may be an effective approach for treating RA.
引用
收藏
页码:2397 / 2412
页数:16
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