A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery

Abstract

Embedding microfluidic architectures with microneedles enables fluid management capabilities that present new degrees of freedom for transdermal drug delivery. To this end, fabrication schemes that can simultaneously create and integrate complex millimeter/centimeter-long microfluidic structures and micrometer-scale microneedle features are necessary. Accordingly, three-dimensional (3D) printing techniques are suitable candidates because they allow the rapid realization of customizable yet intricate microfluidic and microneedle features. However, previously reported 3D-printing approaches utilized costly instrumentation that lacked the desired versatility to print both features in a single step and the throughput to render components within distinct length-scales. Here, for the first time in literature, we devise a fabrication scheme to create hollow microneedles interfaced with microfluidic structures in a single step. Our method utilizes stereolithography 3D-printing and pushes its boundaries (achieving print resolutions below the full width half maximum laser spot size resolution) to create complex architectures with lower cost and higher print speed and throughput than previously reported methods. To demonstrate a potential application, a microfluidic-enabled microneedle architecture was printed to render hydrodynamic mixing and transdermal drug delivery within a single device. The presented architectures can be adopted in future biomedical devices to facilitate new modes of operations for transdermal drug delivery applications such as combinational therapy for preclinical testing of biologic treatments.

Progress in Microneedle-Mediated Protein Delivery

“…This structure allows MNs to interface with larger delivery loads [46,47]. Equally interestingly, stereolithography 3D printing was employed to fabricate-in a single step-hollow MNs interfaced with microfluidic structures within a single device to obtain higher fluid management capabilities for transdermal drug delivery [48].…”

The Fabrication and Application Mechanism of Microfluidic Systems for High Throughput Biomedical Screening: A Review

“…The patterns on PC substrates were fabricated using an injection molding machine with a high-precision nickel mold (shown in Figure 1A) [40]. Yeung et al developed a microfluidic device with a hollow microneedle architecture using resin by 3D-printing for the purpose of transdermal drug delivery [41]. Further, TPE is an advanced material for microfluidic fabrication because it is highly reproducible and is capable of sealing to other materials, and is especially able to bond with glass [42].…”

“…In general, ECM in HTBMS performs three functions in the system: (1) providing a real-like microenvironment in HTBMS for cell growth, even differentiating organ structures; (2) building drug gradients in HTBMS, utilizing the high penetrability of ECM; (3) the ECM is cured into an array with a special pattern for building high-throughput cell aggregation models, spheroid models, and even tissue/organ models. [41]. Further, TPE is an advanced material for microfluidic fabrication because it is highly reproducible and is capable of sealing to other materials, and is especially able to bond with glass [42].…”

Microneedle-based bioassays

“…These 3D printed and microuidic-integrated hollow MNs can be adopted in future biomedical devices targeted at transdermal drug delivery and biouid extraction, the latter being an essential element in bioassays. 39 Aside from fabricating MNs directly, the most commonly used approach for MN fabrication is molding, which can realize accurate duplicates of designed structures and allow the use of various materials otherwise unsuitable for etching and 3D…”