Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications
Structural and microfluidic analysis of hollow side-open polymeric microneedles for transdermal drug delivery applications
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DOI：
10.1007/s10404-009-0467-9
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发表时间：
2010-03-01
影响因子：
2.8
通讯作者：
Afzulpurkar, Nitin
中科院分区：
文献类型：
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作者：
Bodhale, Dhananjay W.;Nisar, Asim;Afzulpurkar, Nitin
在本文中，我们提出了一种新的中空，面外的聚合物微针，具有圆柱形的侧面开孔，用于透皮给药（TDD）应用。本文首先对现有的微针设计和分析工作进行了详细的文献综述，为从事基于微机电系统（MEMS）的微针设计和开发的研究人员提供了一个全面的参考，也为那些希望为特定药物输送或生物医学应用选择最佳微针设计的非该领域的研究人员提供了一个来源。然后，根据微针的强度和进口压力下的流量对新设计微针的性能进行了数值表征。所有先前的空心微针设计在管腔部分都有侧开孔，在同一芯片上没有集成的储层。我们提出了一种新的设计，在锥形部分有侧开孔，以确保在皮肤插入时给药。此外，本设计在微针的背面有一个集成的药物储存库。由于基于mems的、中空的、侧开的一体化储层聚合物微针是一个新的研究领域，明显缺乏适用的数学模型来解析预测各种边界条件下的结构和流体流动。这就是为什么有限元（FE）和计算流体动力学（CFD）分析使用ANSYS而不是分析系统来促进制造前的设计优化。对微针阵列的三维模型进行了结构仿真和CFD分析。在应力分析中，研究了微针插皮过程中轴向和横向载荷对微针的影响。分析预测，由于施加的弯曲和轴向载荷的合成应力在安全范围内，低于所提出的微针设计材料的屈服强度。在CFD分析中，对施加进口压力时微针内的流体流速和压降进行了数值和理论研究。CFD分析预测了每个微针通过微针阵列的均匀流动。流量和压降的理论和数值结果吻合较好，从而验证了CFD分析的正确性。针对所提出的微针设计，提出了微热压印和紫外准分子激光等可行的制造技术。本文的理论研究结果为聚合物空心微针的优化设计提供了有价值的基准和预测数据，并可与其他微流控器件成功集成用于TDD应用。
In this paper, we present a new design of hollow, out-of-plane polymeric microneedle with cylindrical side-open holes for transdermal drug delivery (TDD) applications. A detailed literature review of existing designs and analysis work on microneedles is first presented to provide a comprehensive reference for researchers working on design and development of micro-electromechanical system (MEMS)-based microneedles and a source for those outside the field who wish to select the best available microneedle design for a specific drug delivery or biomedical application. Then, the performance of the proposed new design of microneedles is numerically characterized in terms of microneedle strength and flow rate at applied inlet pressures. All the previous designs of hollow microneedles have side-open holes in the lumen section with no integrated reservoir on the same chip. We have proposed a new design with side-open holes in the conical section to ensure drug delivery on skin insertion. Furthermore, the present design has an integrated drug reservoir on the back side of the microneedles. Since MEMS-based, hollow, side-open polymeric microneedles with integrated reservoir is a new research area, there is a notable lack of applicable mathematical models to analytically predict structural and fluid flow under various boundary conditions. That is why, finite element (FE) and computational fluid dynamic (CFD) analysis using ANSYS rather than analytical systems has been used to facilitate design optimization before fabrication. The analysis has involved simulation of structural and CFD analysis on three-dimensional model of microneedle array. The effect of axial and transverse loading on the microneedle during skin insertion is investigated in the stress analysis. The analysis predicts that the resultant stresses due to applied bending and axial loads are in the safe range below the yield strength of the material for the proposed design of the microneedles. In CFD analysis, fluid flow rate and pressure drop in the microneedles at applied inlet pressures are numerically and theoretically investigated. The CFD analysis predicts uniform flow through the microneedle array for each microneedle. Theoretical and numerical results for the flow rate and pressure drop are in close agreement with each other, thereby validating the CFD analysis. For the proposed design of microneedles, feasible fabrication techniques such as micro-hot embossing and ultraviolet excimer laser methods are proposed. The results of the present theoretical study provide valuable benchmark and prediction data to fabricate optimized designs of the polymeric, hollow microneedles, which can be successfully integrated with other microfluidic devices for TDD applications.