{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:53:44Z","timestamp":1781844824360,"version":"3.54.5"},"reference-count":32,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T00:00:00Z","timestamp":1781827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Heilongjiang Touyan Innovation Team Program"},{"name":"Mechanism of Gexia Zhuyu Decoction Against Microcirculation Disorder in the Treatment of Non-alcoholic Fatty Liver Disease Based on Qi and Blood Theory","award":["2020YQ05"],"award-info":[{"award-number":["2020YQ05"]}]},{"name":"Bidirectional Selectivity Study of Acupoints and External Application of Chinese Medicine in the Treatment of Rheumatoid Arthritis Based on \u201cReservoir Response\u201d Effect","award":["82074271"],"award-info":[{"award-number":["82074271"]}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"\n Introduction<\/jats:title>\n The administration of drugs at specific acupoints is a traditional practice in Chinese medicine, yet scientific evidence supporting its pharmacokinetic and pharmacodynamic (PK\/PD) advantages remains limited. This study aimed to evaluate the transdermal absorption and therapeutic effects of miRNA55 when delivered via microneedles at different acupoints in a rabbit model of rheumatoid arthritis (RA).<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n An RA model was established in New Zealand rabbits using ovalbumin-Freund\u2019s complete adjuvant emulsion. miRNA55 was encapsulated in cationic liposomes and combined with hyaluronic acid for microneedle preparation. Microneedles were applied at classical acupoint (ST36), atypical acupoints (GB34), and non-acupoint areas above the knee joint of the rabbits (avoiding ST35). Drug concentrations in the joint cavity fluid were assessed by microdialysis and enzyme-linked immunosorbent assay (ELISA). The encapsulation rate and\n in vitro<\/jats:italic>\n release of miRNA55 were analyzed by UV spectrophotometry. PK\/PD modeling was conducted using WinNonlin 8.1, with IL-1\u03b2, TNF-\n \u03b1<\/jats:italic>\n , and IL-6 as pharmacodynamic markers. The protein expression of TNF-\u03b1, MMP-1, and MMP-3 was assessed using western blotting (WB), and histopathological changes in the synovial tissue were observed by hematoxylin\u2013eosin (H&amp;E) staining.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n miRNA55 concentrations in the joint cavity were the highest in the ST36 group, followed by the GB34 and non-acupoint groups. This observation indicated that the degree of drug absorption. PK\/PD modeling showed higher efficacy value for ST36 across all three cytokines. For IL-1\u03b2, Emax model for ST36 was\n \n \n \n E<\/mml:mi>\n =<\/mml:mo>\n \n \n 81.09<\/mml:mn>\n \n C<\/mml:mi>\n e<\/mml:mi>\n <\/mml:msub>\n <\/mml:mrow>\n \n 169.56<\/mml:mn>\n +<\/mml:mo>\n \n C<\/mml:mi>\n e<\/mml:mi>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:mfrac>\n <\/mml:math>\n <\/jats:inline-formula>\n ; for TNF-\n \u03b1<\/jats:italic>\n ,\n \n \n E<\/mml:mi>\n =<\/mml:mo>\n \n \n 70.35<\/mml:mn>\n \n C<\/mml:mi>\n e<\/mml:mi>\n <\/mml:msub>\n <\/mml:mrow>\n \n 136.15<\/mml:mn>\n +<\/mml:mo>\n \n C<\/mml:mi>\n e<\/mml:mi>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:mfrac>\n <\/mml:math>\n <\/jats:inline-formula>\n ; and for IL-6,\n \n \n E<\/mml:mi>\n =<\/mml:mo>\n \n \n 69.93<\/mml:mn>\n \n C<\/mml:mi>\n e<\/mml:mi>\n <\/mml:msub>\n <\/mml:mrow>\n \n 167.88<\/mml:mn>\n +<\/mml:mo>\n \n C<\/mml:mi>\n e<\/mml:mi>\n <\/mml:msub>\n <\/mml:mrow>\n <\/mml:mfrac>\n <\/mml:math>\n <\/jats:inline-formula>\n , all higher than those observed in the GB34 and non-acupoint groups. WB analysis confirmed lower expression level of inflammatory proteins in the ST36 group. H&amp;E staining showed reduced synovial erosion and lymphokine infiltration in the ST36 group compared to those in the other two groups.\n <\/jats:p>\n <\/jats:sec>\n \n Discussion<\/jats:title>\n This study demonstrates that transdermal administration of miRNA55 via microneedle at specific acupoints enhances drug absorption and improves therapeutic outcomes in a rabbit model of RA. These findings support the traditional concept of acupoint specificity and offer a scientific basis for integrating acupoint-based drug delivery in modern RA treatment strategies.<\/jats:p>\n <\/jats:sec>","DOI":"10.3389\/fneur.2026.1754856","type":"journal-article","created":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T04:30:38Z","timestamp":1781843438000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Experimental verification and PK\/PD modeling of selective drug absorption via acupoint administration in rabbit model of rheumatoid arthritis"],"prefix":"10.3389","volume":"17","author":[{"given":"Zhoubo","family":"Yu","sequence":"first","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[{"name":"Basic Medical College, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhao","family":"Zhang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"He","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming","family":"Liu","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pengfei","family":"Ren","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiannan","family":"Meng","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rui","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Pharmacy, Heilongjiang University of Chinese Medicine","place":["Harbin, Heilongjiang, China"]},{"name":"Key Laboratory of Basic and Application Research of Beiyao, Heilongjiang University of Chinese Medicine, Ministry of Education","place":["Harbin, Heilongjiang, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,19]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1016\/j.mpmed.2018.01.008","article-title":"Clinical features 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