Journal
INTERNATIONAL JOURNAL OF PHARMACEUTICS
Volume 563, Issue -, Pages 91-100Publisher
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijpharm.2019.03.033
Keywords
Dissolving microneedles; Neurotoxin; Rheumatoid Arthritis; Transdermal delivery; Biocomfortable
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Funding
- National Natural Science Foundation of China [81503256]
- Natural Science Foundation of Zhejiang Province [LQ19H280004, LY18H280001]
- Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province [2018ZQ013]
- Science and Technology Innovation Team Project of Zhejiang Province [2017R410056]
- Science and Technology Top Talent Support Project, Department of Education, Guizhou Province [Qiankehe KY[2017]074]
- Guizhou Provincial Department of Science and Technology [Qiankehe talent-cultivating platform [2017]5735-26]
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This study is directed towards the gentle transdermal delivery of Neurotoxin (NT) and study of the treatment of Rheumatoid Arthritis (RA) in rats by NT loaded dissolving Microneedles (DMNs-NT). The DMNs-NT fabrication involved a two-step centrifugation method. The quadrangular pyramid shape needles had great mechanical strength. The upper part of the needle contained 15.4 +/- 0.5 mu g of drug per patch. Blank DMNs showed favorable biocompatibility and low toxicity on the chondrocyte cells. Both NT and DMNs-NT displayed anti-inflammatory capabilities ex-vitro. The results of ex-vitro evaluation of DMNs the skin penetration depth of DMNs-NT rats was higher than 70 mu m and the cumulative penetration of NT in DMNs could reach 95.8% in 4 h, whereas, the NT solution could barely penetrate the skin, thereby proving the favorable facilitation of NT transdermal delivery. The needle structure dissolved completely after 10 min in vivo and the channel on the Stratum Corneum (SC) was closed after 6 h. There was no significant adverse reaction on the skin after 15 days of administration. The pharmacodynamic study showed that DMNs-NT significantly reduced the toe swelling of RA rats and reduced the levels of TNF-alpha and IL-1 beta in serum to alleviate the injury of the ankle joints. DMNs-NT held favorable stability in 3 months. All these results established that DMNs-NT could penetrate the skin of rats in a biocompatible manner, and have a strong therapeutic effect on rat RA by transdermal delivery.
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