Spatially controlled coating of continuous liquid interface production microneedles for transdermal protein delivery
Spatially controlled coating of continuous liquid interface production microneedles for transdermal protein delivery
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DOI：
10.1016/j.jconrel.2018.05.042
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发表时间：
2018-08-28
影响因子：
10.8
通讯作者：
DeSimone, Joseph M.
中科院分区：
文献类型：
--
作者：
Caudill, Cassie L.;Perry, Jillian L.;DeSimone, Joseph M.
微针贴片是一种以微创方式穿透皮肤的微米级投射阵列，是一种很有前途的经皮输送治疗性蛋白质的工具。然而，目前的微针制造技术在快速制造微针的能力和对微针设计参数的高度控制方面受到限制。我们之前已经展示了使用新型增材制造技术连续液界面生产（CLIP）制造具有一系列成分和几何形状的微针贴片的能力。在这里，我们建立了一种以空间控制的方式浸涂蛋白质货物的CLIP微针的方法。用CLIP制备微针涂层面罩装置，并利用模型蛋白牛血清白蛋白、卵白蛋白和溶菌酶涂覆聚乙烯乙二醇基CLIP微针。设计的涂层屏蔽装置用于控制涂层蛋白货物在微针上的空间沉积和装载。CLIP微针在溶液中和插入猪皮后都能迅速释放包裹的蛋白质。模型酶溶菌酶在整个CLIP微针包被过程中保持其活性，并且在应用包被的CLIP微针后观察到牛血清白蛋白在全层猪皮肤上的渗透。蛋白质包被的CLIP微针被应用于活小鼠，并显示蛋白质货物在皮肤中持续保留超过72小时。这些结果证明了多功能包被平台用于制备用于经皮治疗递送的精确包被微针的实用性。
Microneedle patches, arrays of micron-scale projections that penetrate skin in a minimally invasive manner, are a promising tool for transdermally delivering therapeutic proteins. However, current microneedle fabrication techniques are limited in their ability to fabricate microneedles rapidly and with a high degree of control over microneedle design parameters. We have previously demonstrated the ability to fabricate microneedle patches with a range of compositions and geometries using the novel additive manufacturing technique Continuous Liquid Interface Production (CLIP). Here, we establish a method for dip coating CLIP microneedles with protein cargo in a spatially controlled manner. Microneedle coating mask devices were fabricated with CLIP and utilized to coat polyethylene glycol-based CLIP microneedles with model proteins bovine serum albumin, ovalbumin, and lysozyme. The design of the coating mask device was used to control spatial deposition and loading of coated protein cargo on the microneedles. CLIP microneedles rapidly released coated protein cargo both in solution and upon insertion into porcine skin. The model enzyme lysozyme was shown to retain its activity throughout the CLIP microneedle coating process, and permeation of bovine serum albumin across full thickness porcine skin was observed after application with coated CLIP microneedles. Protein-coated CLIP microneedles were applied to live mice and showed sustained retention of protein cargo in the skin over 72 h. These results demonstrate the utility of a versatile coating platform for preparation of precisely coated microneedles for transdermal therapeutic delivery.