Enhanced efficacy of brucine dissolving-microneedles as a targeted delivery system in rheumatoid arthritis treatment: a comprehensive pharmacokinetic-pharmacodynamic analysis.
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引用次数: 0
Abstract
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.
我们之前的研究表明，布鲁宾溶解微针（Bru-DMNs）在治疗类风湿性关节炎（RA）方面具有疗效。通过 DMNs 给药的布鲁氨酸可以绕过一些与口服和全身给药相关的问题，包括广泛的酶活性、肝脏代谢，以及在通过皮下注射针进行全身给药的情况下，因注射和针刺损伤造成的疼痛。然而，Bru-DMNs 抗 RA 的基本机制尚未在药代动力学-药效学（PK-PD）层面上得到深入研究。本研究开发了一种基于微透析的方法，结合超高效液相色谱-串联质谱法，对完全清醒的 RA 大鼠的血液和关节腔进行同步连续采样和定量分析。获得的数据采用 PK-PD 分析方法进行分析。与在血液中给药相比，通过微针给药的布鲁在关节腔中的分布更广，保留时间更长。布鲁的作用效果与其在作用部位的浓度之间存在间接相关性。本研究探讨了Bru-DMNs抗RA的机制，并建立了一种可视化方法来表达Bru-DMNs抗RA的PK-PD关系。这项研究有助于深入了解经皮给药治疗 RA 具有潜在副作用的药物的作用机制。
期刊介绍：
The journal provides a unique forum for scientific publication of high-quality research that is exclusively focused on translational aspects of drug delivery. Rationally developed, effective delivery systems can potentially affect clinical outcome in different disease conditions.
Research focused on the following areas of translational drug delivery research will be considered for publication in the journal.
Designing and developing novel drug delivery systems, with a focus on their application to disease conditions;
Preclinical and clinical data related to drug delivery systems;
Drug distribution, pharmacokinetics, clearance, with drug delivery systems as compared to traditional dosing to demonstrate beneficial outcomes
Short-term and long-term biocompatibility of drug delivery systems, host response;
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Devices for drug delivery and drug/device combination products.
In addition to original full-length papers, communications, and reviews, the journal includes editorials, reports of future meetings, research highlights, and announcements pertaining to the activities of the Controlled Release Society.
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