Structural characterisation and transdermal delivery studies on sugar microneedles: Experimental and finite element modelling analyses

Abstract

Dissolving microneedles are especially attractive for transdermal drug delivery as they are associated with improved patient compliance and safety. Furthermore, microneedles made of sugars offer the added benefit of biomolecule stabilisation making them ideal candidates for delivering biological agents such as proteins, peptides and nucleic acids. In this study, we performed experimental and finite element analyses to study the mechanical properties of sugar microneedles and evaluate the effect of sugar composition on microneedle ability to penetrate and deliver drug to the skin. Results showed that microneedles made of carboxymethylcellulose/maltose are superior to those made of carboxymethylcellulose/trehalose and carboxymethylcellulose/sucrose in terms of mechanical strength and the ability to deliver drug. Buckling was predicted to be the main mode of microneedle failure and the order of buckling was positively correlated to the Young's modulus values of the sugar constituents of each microneedle.

Evaluation of geometrical effects of microneedles on skin penetration by CT scan and finite element analysis

“…Donelly et al 29 first demonstrated the versatility of this technique in preparing conical shaped microneedle arrays of varied geometrical parameters such as height, interspacing and base diameter. In a previous work we used laser micromachining to prepare 18x18 arrays of conical shape microneedles with the aim of investigating the effect of material on skin penetration 12 . In this work we used laser micromachining to prepare microneedles of varying base geometry whilst keeping other factors (base diameter, interspace, microneedle length) the same.…”

“…The bed-of-nails effect begins to have a negative effect on penetration, at interspacing values smaller than 150 μm 14,15,17 . Furthermore, microneedles made from material of high Young's modulus, showed enhanced mechanical properties and penetration characteristics 12,13 .…”

“…Due to its viscoelastic nature 5 , skin is easily deformed when microneedles are applied to its surface, and therefore, the microneedle design and constructional material will determine the extent of skin penetration by the microneedles, and in the resulting effect on drug permeability 2 . The most critical factors for microneedle skin penetration were attributed to needle length and density 6,7 , tip and base diameter [8][9][10] and microneedle material [11][12][13] . In addition, the use of an injection applicator was found to greatly enhance penetration with a critical role on force and velocity of microneedle injection [14][15][16] .…”

“…This can be during the selection of the sampling area, and also, of possible alterations in the structure of the skin after the microneedles are removed, as expected for hyperelastic materials such as the skin 20,21 . To limit the problems associated with histological processing, whole tissue techniques such as confocal microscopy 12,22,23 and optical coherence tomography (OCT) 15,24,25 , are often implemented. Both techniques offer the advantage of in vivo application, with OCT having the added benefit of achieving higher penetration depths of approximately 2.0 mm, compared with 0.25 mm of confocal microscopy 15 .…”

A New Paradigm for Numerical Simulation of Microneedle-Based Drug Delivery Aided by Histology of Microneedle-Pierced Skin

“…There are plenty of previous studies which have used 3D MNs 518 model to simulate diffusion in TDD [38]. However, our 3D model is constructed from the pores 519 created by MNs instead of building a model using the shape of MNs.…”