Microneedles for Theranostics

Microneedle (MN) arrays were developed to provide a minimally invasive approach to detect biomarkers and deliver drugs into the ISF. Solid, hollow, and dissolvable MNs have been fabricated for various applications and have been evaluated to be very advantageous. These advantages include better patient compliance dur to painless and non-invasive administration, improved permeability and efficiency and provide targeted drug delivery by varying MN dimensions to specific regions in the skin. Techniques to fabricate MNs vary based on the material and potential application requirements. The most common techniques are micro-moulding, wet and dry etching with lithography and laser cutting. Micro-moulding fabrication have been utilized to produce various polymer, hydrogel and dissolvable MNs by filling prepared moulds with a liquid formulation. Alternatively, lithography using wet and dry etching have been used to fabricate MNs. A mask is used as a template for generating the desired pattern on a wafer surface using either a positive or negative photoresist to generate the desired pattern. These wafers are then etched using a strong caustic agent or an etcher. Finally, laser cutting techniques have been used to produce metal MN using a computer aided design to create the desired shape and dimensions. In recent studies, MNs have been created for a wide range of diagnostic and drug delivery applications. A wide range of MNs have been adapted for a variety of disease treatments such as cancer, arthritis and ophthalmic disorders. As diabetes mellitus effects approximately 30 million people and glucose monitoring has advanced from the initial self-monitoring of blood glucose levels to glucose biosensors, a high demand for MNs to be modified for diabetes management has been emphasized. This thesis details the fabrication of MNs using silicon, polyvinylpyrollidone (PVP) and polycarbonate for sensing and drug delivery. Silicon wafers with the combination of photolithography and deep-reactive ion etching (DRIE) techniques are used to create solid and hollow MNs. The MN arrays have sharp tips that provide eased insertion and injectable capabilities. Polycarbonate and PVP MNs were manufactured using micro-moulding techniques to create solid and dissolvable MNs respectively. These MNs were characterized to determine their penetration capabilities through the stratum corneum (SC) to providecontrolled transdermal drug delivery and diagnose biomarkers within the interstitial fluid (ISF).For diagnostic applications, the polycarbonate MNs were modified for glucose sensing using first generation sending strategies wherein oxygen in used as the electron acceptor and the levels of glucose is proportional to the peroxide produced. To determine drug delivery capabilities of MNs, the solid polycarbonate and silicon MNs employed ‘poke and patch’ techniques with the use of a Franz cell to show calcein and FITC-insulin delivery over 24 hours. On the other hand, for drug delivery through the dissolvable PVP MNs, ‘poke and dissolve’ techniques were analysed with the use of Franz cells to show the release of encapsulated calcein and FITC-insulin within the polymeric matrix over 24 hours. The arrays were either left blank for basal drug delivery or metallised with silver for controlled drug delivery using the metals breakdown potential.