Planejamento fatorial para obtenção de arranjos de microagulhas por impressão 3D com potencial uso em drug delivery

Abstract

The present study aimed to develop, characterise, and optimise microneedle (MN) arrays using three-dimensional printing based on liquid crystal display (LCD) technology. MNs represent an alternative, minimally invasive, and painless route for the administration of drugs and nutrients, such as vitamin B12 and insulin, overcoming limitations associated with the oral route, including low bioavailability, as well as those related to conventional injections, such as pain and tissue trauma. The study focused on the geometric optimisation of resin-based master moulds with a hybrid geometry composed of a cubic base and a pyramidal tip, prior to the production of silicone micromoulds intended for the fabrication of polymeric MNs. The adopted methodology was based on an experimental design employing Response Surface Methodology (RSM), considering printing angle and exposure time as independent factors, and MN length, depth, height, and tip definition as response variables. Statistical analysis, performed using analysis of variance and Pareto charts, identified exposure time as the most significant factor, exhibiting a parabolic behaviour across all evaluated responses, with a maximum point occurring prior to overcuring. Although secondary, the printing angle also influenced the responses analysed. Application of the Derringer–Suich desirability function for multi-objective optimisation indicated optimal operating conditions associated with a moderate exposure time and an intermediate printing angle. However, morphological analysis revealed that, due to the low layer thickness adopted (10 micrometres), the MNs exhibited poor geometric fidelity under all studied conditions. It is therefore concluded that the experimental design approach was effective in identifying critical process parameters, while also indicating the need to adjust the layer thickness to values greater than 10 micrometres in future studies in order to improve the geometric accuracy of the microstructures.