超声导入对酮洛芬凝胶药物经皮促透效果的研究

Study on the Enhanced Transdermal Permeation of Ketoprofen Gel Induced by Ultrasound

关键词:  酮洛芬凝胶  超声导入  离体渗透  药效学  药物动力学

Key words:  ketoprofen gel  ultrasound-assisted delivery  in vitro permeation  pharmacodynamics  pharmacokinetics

摘要:

目的 酮洛芬是一种非甾体抗炎药,口服给药存在胃肠道不良反应的问题。经皮给药可避免胃肠道刺激,但经皮制剂自身透过率较低。本研究采用低频低功率超声作为物理经皮促透手段,研究其对酮洛芬凝胶经皮吸收的促进作用。方法 以酮洛芬凝胶为模型药物,比较超声处理组和未处理组的离体经皮渗透量。并建立大鼠胶原蛋白致炎模型,评价两组药效学差异。最后通过药物动力学研究,观察超声对酮洛芬凝胶体内过程的影响。结果 与未处理组相比,超声处理可将酮洛芬凝胶在给药24 h的离体皮肤累积渗透量提高3.5倍；使药动学中的AUC0-t从 4289.02±763.58ng·h/mL提高至11301±3386 ng·h/mL,Tmax从6.0±1.4 h提前至3.00±2.0 h,均存在显著性差异(p<0.05)；另外,超声处理4h后能特别显著地提高酮洛芬凝胶在大鼠炎症模型中的抗炎作用,快速有效地降低蛋清致炎后的肿胀程度。结论 本研究从皮肤渗透试验、药效学评价和药动学等方面证实了低频超声可显著提高酮洛芬凝胶的经皮吸收量和吸收速率,增强其药效强度,是酮洛芬凝胶经皮给药的有效促进手段。

Abstract:

OBJECTIVE Ketoprofen, a non-steroidal anti-inflammatory drug, is associated with significant gastrointestinal side effects when taken orally. This research investigates the potential of low-frequency, low-power ultrasound to enhance the transdermal absorption and efficacy of ketoprofen gel, aiming to bypass the gastrointestinal route. METHODS We compared the transdermal permeation of ketoprofen gel in vitro between ultrasound-treated and untreated samples. Additionally, a rat model of collagen-induced inflammation provided a basis for evaluating pharmacodynamic differences. Pharmacokinetic studies further elucidated the effects of ultrasound on ketoprofen gel's penetration process. RESULTS Ultrasound treatment enhanced the cumulative transdermal permeation of ketoprofen gel by 3.5-fold over 24 hours compared to untreated gel. Significant pharmacokinetic improvements included a 2.6-fold rise in AUC0-t (from 4289.02±763.58 to 11301±3386 ng·h/mL) and a reduction in Tmax from 6.0±1.4 h to 3.0±2.0 h (p<0.05). Ultrasound notably improved the gel's anti-inflammatory effects in the rat model, effectively and rapidly reducing inflammation-induced swelling. CONCLUSION This study confirmed that low-frequency ultrasound can significantly improve the amount and rate of transdermal absorption of ketoprofen gel and enhance its pharmacological potency, from the aspects of skin permeation tests, pharmacodynamic evaluation, and pharmacokinetic studies, which is an effective penetration enhancer for transdermal administration of ketoprofen gel.