Construction of ultrasound-triggered amiodarone sustained-release microneedle patch and its application in the treatment of atrial fibrillation
CAO Qin
LIU Xuan
CHENG Sen-zhong
LI Yang
Abstract：Objective To prepare an ultrasound-triggered amiodarone sustained-release microneedle patch and further investigate the application effect of amiodarone sustained-release microneedles in the treatment of atrial fibrillation(AF).Methods Ultrasound-triggered amiodarone sustained-release microneedle patches were prepared,and the drug loading was determined by high-performance liquid chromatography(HPLC);microneedle morphology,stability and skin puncture performance were examined by light microscopy,scanning electron microscopy and skin puncture experiments;microneedle in vitro permeability was measured by the Franz diffusion cell method;and microneedle treatment in a rat model of atrial fibrillation was observed by a pharmacodynamic experiment.Results The microneedle array prepared in this study was well-arranged and complete,with no bubbles on the backing,sharp and complete needle shape without breakage,good morphology,and an average drug loading of(4.67±0.51)μg at the needle tip.The microneedle had good puncture performance,with acceptable needle tip hardness and good dissolution ability.The results of in vitro transdermal penetration showed that the release of the two solutions was relatively slow in the first 0-6 hours,significantly increased in the 8-24 hours,and sharply increased in the 24-36 hours.The cumulative release amount was the highest at 72 hours,and the cumulative release curve of amiodarone suspension was significantly higher than that of amiodarone liposome solution in the 8-72 hours.The pharmacodynamic results showed that ultrasound-triggered amiodarone sustained-release microneedle patch could delay the induction time of atrial fibrillation in rats[(7.52±1.26)s vs.(5.75±1.14)s],shorten the duration of atrial fibrillation[(4.21±0.89)s vs.(6.32±1.02)s],improve the cardiac function of rats[left atrial diameter was(3.52±0.50)s vs.(4.11±0.35)s,diastolic interventricular septal thickness was(2.24±0.18)s vs.(2.58±0.3),systolic interventricular septal thickness was(3.11±0.32)s vs.(3.59±0.50)].The results of tissue drug content showed that the content of amiodarone increased significantly in the atria of model rats,while the content of amiodarone decreased significantly in the plasma,lung,liver,kidney and spleen.Conclusion The prepared ultrasound-triggered amiodarone sustained-release microneedle patch has good performance,which promotes the transdermal delivery of amiodarone,owns good sustained-release performance,and has good clinical application prospects.
Keywords：UltrasoundAmiodaroneMicroneedle patchAtrial fibrillation
Publication Date：2024-08-10
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：6( 763-768 )