Poster X2 - Engineering hydrogel-forming microneedle patches for intradermal drug delivery

Introduction: Microneedle patches, small arrays of micron-sized needles backed by a physical base for application, represent a significant advancement in cutaneous drug delivery. Initially described in the 1970s, these patches circumvent the barrier of the stratum corneum, the skin's outermost layer, enabling direct drug delivery into the dermis instead of relying on passive diffusion from topical application. This technique not only reduces dosing and delivery site variability associated with traditional cutaneous patches and needle-based injections but also facilitates a mostly painless and self-administered application, thus improving patient compliance. Here, we designed microneedle patches made from various hydrogel biomaterials suitable for clinical dermatology applications. Our objectives include engineering and characterizing these patches mechanically and microscopically. We are particularly focused on hydrogels formed via reversible, dynamic bonding, using naturally-occurring, biodegradable polymer backbones, which are known for their safe interaction with and effective degradation in the extracellular matrix of the dermis. We optimized fabrication at heights of 600 μm and 800 μm to ensure effective skin penetration through the epidermis with fracture forces of 0.1 N and 3 N. In vivo testing confirmed that these hydrogel-based microneedle patches successfully puncture the stratum corneum and cause hair follicles to cycle into their growth phase, anagen, highlighting their potential as a therapeutic. These patches offer a reliable, effective, and repeatable method for drug delivery, with promising implications for broader dermatological applications.

Materials and

Methods: Hydrogel formulations for microneedle patches were developed using various materials and processes. Gelatin hydrogels were prepared from bovine skin gelatin dissolved in deionized water at 50°C, with concentrations of 10 wt%, 20 wt%, and 30 wt%. The solution underwent centrifugation and vortexing to achieve uniform viscosity.
Microneedle patches were fabricated using Silicone Templates ST-05 and ST-08 from Micropoint Technologies. The molds were pre-vacuumed, filled with the hydrogel formulations, and then centrifuged to ensure consistency. After centrifugation, the hydrogels were dried in a vacuum for 48 hours before demolding to dry out the hydrogels. The mechanical integrity of the patches was tested using an Instron 5564 Tabletop Universal Testing Machine, which applied compression to the needle tips to measure force resistance up to 1.5kN. Additionally, the structural properties of the microneedles were characterized using Scanning Electron Microscopy (SEM) with a TFS Quanta 600 ESEM, providing detailed imaging of the microneedle surfaces.
For in vivo studies, microneedle patches were applied to male C57BL/6 mice at eight weeks, during which their hair is in telogen. After depilation, microneedle patches were applied directly to dorsal skin and occluded under Tegaderm for 10 days after which anagen induction was visualized.

Results, Conclusions, and Discussions: Our study established a reproducible protocol for fabricating microneedle patches, significantly advancing cutaneous drug delivery. We compared two methods: pre-vacuuming molds and combining pre-vacuuming with centrifugation. The latter method proved most effective, producing uniform and robust microneedles across various hydrogel compositions, as confirmed by light microscopy and scanning electron microscopy (SEM). These analyses highlighted the microneedles' sharpness and uniformity, crucial for effective skin penetration without discomfort. Mechanical testing with an Instron machine revealed that microneedles made from 30 wt% gelatin at heights of 600 μm and 800 μm could withstand forces of 2.12N and 0.99N, respectively, indicating their viability for penetrating the stratum corneum effectively. Despite these successes, we encountered challenges related to the hydrogel’s viscosity and thermal sensitivity, which affected the uniformity of patches and could degrade sensitive therapeutic agents. These issues underscore the need for further refinement of hydrogel formulations and the overall fabrication process to enhance the microneedles' practical utility and therapeutic efficacy. Preliminary in vivo studies demonstrated the patches' ability to deliver therapeutic agents effectively, inducing anagen in hair follicles, thus showcasing their potential in clinical settings. Moving forward, we aim to explore a broader range of hydrogel formulations and conduct extensive performance testing. This ongoing research will focus on optimizing the delivery mechanisms and enhancing therapeutic outcomes, striving to maximize the therapeutic potential of microneedle patches. By addressing these challenges and leveraging our findings, microneedle patches can significantly impact drug delivery methods, providing a more effective, targeted, and patient-friendly alternative to traditional approaches. Our continued efforts will likely lead to improvements in personalized medicine, making microneedle patches a cornerstone of innovative drug delivery systems.

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