Gittard Shaun D, Ovsianikov Aleksandr, Monteiro-Riviere Nancy A, Lusk Jason, Morel Pierre, Minghetti Paola, Lenardi Cristina, Chichkov Boris N, Narayan Roger J
Joint Department of Biomedical Engineering, University of North Carolina and North Carolina State University, Raleigh, North Carolina, USA.
J Diabetes Sci Technol. 2009 Mar 1;3(2):304-11. doi: 10.1177/193229680900300211.
Microneedle-mediated drug delivery is a promising method for transdermal delivery of insulin, incretin mimetics, and other protein-based pharmacologic agents for treatment of diabetes mellitus. One factor that has limited clinical application of conventional microneedle technology is the poor fracture behavior of microneedles that are created using conventional materials and methods. In this study polymer microneedles for transdermal delivery were created using a two-photon polymerization (2PP) microfabrication and subsequent polydimethylsiloxane (PDMS) micromolding process.
Solid microneedle arrays, fabricated by means of 2PP, were used to create negative molds from PDMS. Using these molds microneedle arrays were subsequently prepared by molding eShell 200, a photo-reactive acrylate-based polymer that exhibits water and perspiration resistance.
The eShell 200 microneedle array demonstrated suitable compressive strength for use in transdermal drug delivery applications. Human epidermal keratinocyte viability on the eShell 200 polymer surfaces was similar to that on polystyrene control surfaces. In vitro studies demonstrated that eShell 200 microneedle arrays fabricated using the 2PP microfabrication and PDMS micromolding process technique successfully penetrated human stratum corneum and epidermis.
Our results suggest that a 2PP microfabrication and subsequent PDMS micromolding process may be used to create microneedle structures with appropriate structural, mechanical, and biological properties for transdermal drug delivery of insulin and other protein-based pharmacologic agents for treatment of diabetes mellitus.
微针介导的药物递送是一种很有前景的经皮递送胰岛素、肠促胰岛素类似物及其他基于蛋白质的药物制剂以治疗糖尿病的方法。传统微针技术临床应用受限的一个因素是使用传统材料和方法制造的微针断裂性能不佳。在本研究中，采用双光子聚合（2PP）微加工及后续聚二甲基硅氧烷（PDMS）微成型工艺制造用于经皮递送的聚合物微针。
通过2PP制造的实心微针阵列用于制作PDMS的阴模。使用这些模具，随后通过模塑eShell 200（一种具有防水和抗汗性能的光反应性丙烯酸基聚合物）制备微针阵列。
eShell 200微针阵列表现出适用于经皮给药应用的抗压强度。eShell 200聚合物表面上的人表皮角质形成细胞活力与聚苯乙烯对照表面上的相似。体外研究表明，采用2PP微加工和PDMS微成型工艺技术制造的eShell 200微针阵列成功穿透了人角质层和表皮。
我们的结果表明，2PP微加工及后续PDMS微成型工艺可用于制造具有适当结构、机械和生物学特性的微针结构，用于经皮递送胰岛素及其他基于蛋白质的药物制剂以治疗糖尿病。
