Division of Pharmacoengineering and Molecular Pharmaceutics, Eshelman School of Pharmacy, University of North Carolina, Chapel Hill, NC 27599, USA.
Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, NC 27599, USA.
J Control Release. 2018 Aug 28;284:122-132. doi: 10.1016/j.jconrel.2018.05.042. Epub 2018 Jun 9.
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.
微针贴剂是一种由微米级突起阵列组成的工具,以微创的方式穿透皮肤,是透皮递药治疗蛋白的有前途的工具。然而,目前的微针制造技术在快速制造微针和对微针设计参数进行高度控制方面存在局限性。我们之前已经证明了使用新型增材制造技术连续液相界面生产 (CLIP) 制造具有多种成分和几何形状的微针贴剂的能力。在这里,我们建立了一种以空间控制方式在蛋白质货物上涂覆 CLIP 微针的方法。使用 CLIP 制造微针涂覆掩模装置,并利用其在聚乙二醇基 CLIP 微针上涂覆模型蛋白牛血清白蛋白、卵清蛋白和溶菌酶。涂覆掩模装置的设计用于控制涂覆蛋白货物在微针上的空间沉积和加载。CLIP 微针在溶液中和插入猪皮后迅速释放涂覆的蛋白货物。模型酶溶菌酶在整个 CLIP 微针涂覆过程中保持其活性,并且在用涂覆的 CLIP 微针应用后观察到牛血清白蛋白渗透到猪皮全层。涂覆蛋白的 CLIP 微针应用于活小鼠,并在皮肤中显示出 72 小时以上的蛋白货物持续保留。这些结果表明,这种多功能的涂层平台可用于制备用于透皮治疗递送的精确涂覆微针。
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