Fang Wei1, Qiuyue Wang1, Hang Liu1, Xuejing Yang1, Wenyu Cao1, Weiman Zhao1, Yingying Li1, Lijie Zheng1, Tao Ma1,2, Qingqing Wang1,2,3. 1. School of Pharmacy, Bengbu Medical College, Bengbu, Anhui Province, 233030, People's Republic of China. 2. Engineering Research Center for Biochemical Pharmaceuticals of Anhui Province, Bengbu Medical College, Bengbu, Anhui Province, 233030, People's Republic of China. 3. Bengbu BBCA Medical Science Co., Ltd., Bengbu, Anhui Province, 233030, People's Republic of China.
Abstract
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.
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.
Authors: Alejandro Artacho; Sandrine Isaac; Renuka Nayak; Alejandra Flor-Duro; Margaret Alexander; Imhoi Koo; Julia Manasson; Philip B Smith; Pamela Rosenthal; Yamen Homsi; Percio Gulko; Javier Pons; Leonor Puchades-Carrasco; Peter Izmirly; Andrew Patterson; Steven B Abramson; Antonio Pineda-Lucena; Peter J Turnbaugh; Carles Ubeda; Jose U Scher Journal: Arthritis Rheumatol Date: 2021-05-02 Impact factor: 10.995
Authors: Liana Fraenkel; Joan M Bathon; Bryant R England; E William St Clair; Thurayya Arayssi; Kristine Carandang; Kevin D Deane; Mark Genovese; Kent Kwas Huston; Gail Kerr; Joel Kremer; Mary C Nakamura; Linda A Russell; Jasvinder A Singh; Benjamin J Smith; Jeffrey A Sparks; Shilpa Venkatachalam; Michael E Weinblatt; Mounir Al-Gibbawi; Joshua F Baker; Kamil E Barbour; Jennifer L Barton; Laura Cappelli; Fatimah Chamseddine; Michael George; Sindhu R Johnson; Lara Kahale; Basil S Karam; Assem M Khamis; Iris Navarro-Millán; Reza Mirza; Pascale Schwab; Namrata Singh; Marat Turgunbaev; Amy S Turner; Sally Yaacoub; Elie A Akl Journal: Arthritis Care Res (Hoboken) Date: 2021-06-08 Impact factor: 5.178