Mechanics of microneedle penetration into skin for drug delivery

Joyce, Rachael 2024. Mechanics of microneedle penetration into skin for drug delivery. PhD Thesis, Cardiff University. Item availability restricted.

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Abstract

Microneedle-based drug delivery systems have gained attention as a minimally invasive alternative to conventional hypodermic needles, particularly for vaccination and transdermal drug delivery. Their potential lies in reduced pain, ease of administration, and the ability to bypass the skin’s stratum corneum barrier. However, challenges remain in optimising microneedle (MN) designs. This study aimed to develop a validated design tool combining Finite Element Analysis (FEA) and digital volume correlation (DVC) to improve the knowledge of needle-skin biomechanics. Current literature highlights gaps in the understanding of high-deformation needle insertion mechanics and limited adoption of advanced imaging techniques, such as μ-CT and subsequent DVC measurement, for evaluating strain distributions through skin substitute during needle penetration. While existing studies have focused on low strain behaviours or geometric optimisations, their findings often rely on assumptions that do not capture the complexity of needle-skin interactions under high strain. To address these gaps, Ecoflex-30 was validated as a skin substitute through mechanical experiments, and two FEMs were developed. Within FEBio a static, low deformation model focusing on indentation was created, and a second dynamic model incorporating a cohesive zone method was implemented to capture high deformations towards full needle puncture modelling. Work of fracture measurements derived from these experiments were directly incorporated into the simulations. Micro focus computed tomography (μ-CT) scans were used to capture deformation data during the initial needle penetration phases (indentation) with a scaled needle of length 1.1 mm. Two sets of tests were conducted: the first focused on a proof of concept for the DVC, and therefore 6 images were taken at intervals of 75 μm to a displacement 375 μm. In the second test, 6 images were taken at intervals of 0 μm, 350 μm, 650 μm, 700 μm, 750 μm and 800 μm to a maximum displacement of 800 μm, representing the large deformation phase just prior to the identified needle puncture point. The results demonstrated strain concentrations at the needle tip and along its edges, indicating potential failure zones essential for creating insertion pathways. Interpolation of DVC data reduced discrepancies between experimental and computational results. This validated the computational model’s initial capabilities and highlighted the benefits of integrating DVC with FEA for evaluating MN designs. This study establishes a foundation for developing MN optimisation tools that incorporate realistic mechanical behaviours and strain distributions through the integration of advanced imaging techniques and material modelling. The research established Ecoflex-30 as a viable skin substitute, demonstrating mechanical properties closely aligned with published in vivo and ex vivo skin data, particularly in terms of stiffness and elasticity (a stiffness of 3.7251 N/mm, shear modulus of 0.0263 MPa and an initial Young’s modulus of 0.0788). By incorporating titanium dioxide particles, the material enables accurate DVC tracking without significantly compromising the mechanical properties (a comparable stiffness of 4.5862 N/mm, shear modulus of 0.0323 MPa and an initial Youngs modulus of 0.0970). The findings underscore the importance of considering high strain behaviours to enhance MN geometry and efficacy. Although not yet ready for direct clinical application, the methods introduced in this research represent a significant step towards the creation of reliable and validated MN design tools that could transform drug delivery and reduce preclinical testing burdens

Item Type:	Thesis (PhD)
Date Type:	Completion
Status:	Unpublished
Schools:	Schools > Engineering
Uncontrolled Keywords:	Microneedles; Finite element analysis; Micro computed tomography; Skin substitutes; High deformation model; Microneedle design tool
Funders:	EPSRC
Date of First Compliant Deposit:	8 May 2025
Last Modified:	08 May 2025 13:19
URI:	https://orca.cardiff.ac.uk/id/eprint/178148

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