Engineering and Development of a Tissue Model for the Evaluation of Microneedle Penetration Ability, Drug Diffusion, Photothermal Activity, and Ultrasound Imaging: A Promising Surrogate to Ex Vivo and In Vivo Tissues

Abstract

Driven by regulatory authorities and the ever-growing demands from industry, various artificial tissue models have been developed. Nevertheless, there is no model to date that is capable of mimicking the biomechanical properties of the skin whilst exhibiting the hydrophilicity/hydrophobicity properties of the skin layers. As a proof-of-concept study, tissue surrogates based on gel and silicone are fabricated for the evaluation of microneedle penetration, drug diffusion, photothermal activity, and ultrasound bioimaging. The silicone layer aims to imitate the stratum corneum while the gel layer aims to mimic the water-rich viable epidermis and dermis present in in vivo tissues. The diffusion of drugs across the tissue model is assessed, and the results reveal that the proposed tissue model shows similar behavior to a cancerous kidney. In place of typical in vitro aqueous solutions, this model can also be employed for evaluating the photoactivity of photothermal agents since the tissue model shows a similar heating profile to skin of mice when irradiated with near-infrared laser. In addition, the designed tissue model exhibits promising results for biomedical applications in optical coherence tomography and ultrasound imaging. Such a tissue model paves the way to reduce the use of animals testing in research whilst obviating ethical concerns.

Keywords: drug delivery models; drug deposition; drug release profiles; microneedle patch penetration; photothermal activity; skin model; tissue models.