微针药物洗脱球囊用于增强血管组织的药物输送。
Microneedle drug eluting balloon for enhanced drug delivery to vascular tissue.
机构信息
Department of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea; Department of Bioengineering, University of California-Los Angeles, Los Angeles, CA 90095, USA; Center for Minimally Invasive Therapeutics (C-MIT), University of California-Los Angeles, Los Angeles, CA 90095, USA; California NanoSystems Institute, University of California-Los Angeles, Los Angeles, CA 90095, USA.
Department of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea.
出版信息
J Control Release. 2020 May 10;321:174-183. doi: 10.1016/j.jconrel.2020.02.012. Epub 2020 Feb 6.
High rates of restenosis and neointimal formation have driven increasing interest in the application of drug eluting balloons (DEB) as counteractive measures for intraluminal drug delivery. The use of DEBs eliminates the need for stents so that serious side effects including in-stent restenosis and stent thrombosis can be avoided and long-term medication of anti-platelet agent is not needed. Despite their benefits, DEBs have poor drug delivery efficiency due to short balloon inflation times (30-60 s) that limit the passive drug diffusion from the balloon surface to the luminal lesion. To increase drug delivery efficiency, a microneedle DEB (MNDEB) was developed by a conformal transfer molding process using a thin polydimethylsiloxane mold bearing a negative array of MNs of 200 μm in height. A MN array composed of UV curable resin was formed onto the surface of DEB, and drugs were coated onto the structure. The mechanical properties of the MN array were investigated and MN penetration into luminal vasculature was confirmed in vivo. An increase in drug delivery efficiency compared to a standard DEB was demonstrated in an in vivo test in a rabbit aorta. Finally, the superior therapeutic efficacy of MNDEBs was evaluated using an atherosclerosis rabbit model.
高复发率和新生内膜形成率促使人们越来越关注药物洗脱球囊（DEB）在腔内药物输送中的应用，作为对抗措施。使用 DEB 可消除支架的需求，从而避免严重的副作用，包括支架内再狭窄和支架内血栓形成，并且不需要长期使用抗血小板药物。尽管具有这些优势，但 DEB 的药物输送效率较差，因为球囊充气时间短（30-60 秒），限制了药物从球囊表面向管腔病变的被动扩散。为了提高药物输送效率，采用保形转移模塑工艺，使用带有负性微针阵列的薄聚二甲基硅氧烷模具（高度为 200μm），开发了微针 DEB（MNDEB）。在 DEB 的表面形成由紫外光固化树脂组成的微针阵列，并将药物涂覆在该结构上。研究了微针阵列的机械性能，并在体内证实了微针穿透管腔血管。在兔主动脉的体内试验中，与标准 DEB 相比，显示出药物输送效率的提高。最后，使用动脉粥样硬化兔模型评估了 MNDEB 的优越治疗效果。
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