(G-264) Interrogation of Dissolving Microneedles with 3D Pathology

Introduction:: In recent decades, dissolving microneedle (DMN) arrays have attracted great interest for intradermal drug delivery applications. To increase their effectiveness, a variety of DMN designs have been explored with different needle geometries, dimensions, materials, and other parameters. A common method to analyze microneedle behavior at the needle-tissue interface has been with 2D histology, which is destructive of the tissue and can only sample a limited region. Here we explore the use of non-destructive 3D pathology, enable by the open-top light-sheet (OTLS) microscopy, to analyze DMN behavior comprehensively across an entire DMN-to-tissue interface.

Materials and Methods::

The microneedles were fabricated using a custom-designed mold with specific dimensions. Different formulations were tested. Ex vivo experiments were conducted on mouse dermal skin using the microneedles. Histology and pathology workflows were employed to analyze the tissue samples, including staining, imaging, and image processing techniques. These workflows generated 2D and 3D datasets for qualitative and quantitative analyses.

Results, Conclusions, and Discussions:: The 3D dataset provides a comprehensive representation of the tissue, while 2D histology may result in artifacts and incomplete information. The 3D pathology workflow preserves microneedle marks without fractures or tissue folds. It also captures both indentation and penetration instances, which may be missed by 2D histology. Additionally, the 3D pathology workflow allows for a complete analysis of the entire microneedle array, offering insights into microneedle behavior. This approach can be used to compare different microneedle designs using quantitative parameters in future studies.

Acknowledgements (Optional): :

We thank the Animal Use Training Sessions at the University of Washington for their generous donation of the mouse carcasses used in this study. Appreciation is also expressed towards Lucila Bella and Wynn Burke from the Department of Medicine and the Department of Laboratory Medicine & Pathology at the University of Washington for their assistance with histological experiments.

The authors acknowledge funding support from the National Institute of Biomedical Imaging and Bioengineering (NIBIB) through R01EB031002 (Liu) and the National Cancer Institute (NCI) through R01CA268207 (Liu).

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