Enhanced efficacy of brucine dissolving-microneedles as a targeted delivery system in rheumatoid arthritis treatment: a comprehensive pharmacokinetic-pharmacodynamic analysis.

Autor: Wang Y; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.; National Engineering Research Center of Miao's Medicines, Guiyang, 550025, China., Yang C; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China., Liu W; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China.; School of Pharmacy, Guizhou Medical University, Guiyang, 561113, China., Zhang Y; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China., Wang Q; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China., Cheng H; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China., Shi J; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China., Yang X; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China., Yang S; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China., Yao X; The Second Affiliated Hospital of Guizhou, University of Traditional Chinese Medicine, Guiyang, 550001, China., Wang Y; Key Laboratory of Pharmaceutics of Guizhou Province, Guizhou Medical University, Guiyang, 550004, China. gywyl@gmc.edu.cn., Song X; School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, China. 392347047@qq.com.; National Engineering Research Center of Miao's Medicines, Guiyang, 550025, China. 392347047@qq.com.
Jazyk: angličtina
Zdroj: Drug delivery and translational research [Drug Deliv Transl Res] 2024 May 05. Date of Electronic Publication: 2024 May 05.
DOI: 10.1007/s13346-024-01606-w
Abstrakt: Our previous studies have shown the therapeutic efficacy of brucine dissolving-microneedles (Bru-DMNs) in treating rheumatoid arthritis (RA). Bru delivered via the DMNs can bypass some of the issues related to oral and systemic delivery, including extensive enzymatic activity, liver metabolism and in the case of systemic delivery via hypodermic needles, pain resulting from injections and needle stick injury. However, the underlying mechanism of Bru-DMNs against RA has not been investigated in depth at the pharmacokinetic-pharmacodynamic (PK-PD) level. In this study, a microdialysis-based method combined with ultra-performance liquid chromatography-tandem mass spectrometry was developed for the simultaneous and continuous sampling and quantitative analysis of blood and joint cavities in fully awake RA rats. The acquired data were analyzed by the PK-PD analysis method. Bru delivered via microneedles showed enhanced distribution and prolonged retention in the joint cavity compared to its administration in blood. The correlation between the effect of Bru and its concentration at the action site was indirect. In this study, we explored the mechanism of Bru-DMNs against RA and established a visualization method to express the PK-PD relationship of Bru-DMNs against RA. This study provides insights into the mechanism of action of drugs with potential side effects administered transdermally for RA treatment.
(© 2024. Controlled Release Society.)
Databáze: MEDLINE
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