title: 3D printed Microneedles for Transdermal Drug Delivery
Creators: name: Oikonomidou, Sofia Nikoleta
Publisher: name: University of Kent
Year: 2022

description: 3D printing is a revolutionary manufacturing and prototyping technology that has altered the outlooks of numerous industrial and scientific fields since its introduction. Recently, it has attracted attention for its potential as a manufacturing tool for transdermal microneedles for drug delivery. In the present thesis, the 3D printability of solid and hollow microneedles via photopolymerisation-based 3D printing was investigated, aiming at establishing robust manufacturing strategies for reproducible, mechanically strong and versatile microneedles. The developed microneedles were employed as drug delivery systems for the treatment of diabetes via insulin administration. Solid microneedles featuring different geometries were designed and 3D printed. It was demonstrated that the printing and post-printing parameters affected the printed quality, a finding that was employed to optimise the manufacturing strategy. Microneedle geometry was also found to have an impact on the piercing and fracture behaviour; however all microneedle designs were found to be mechanically safe upon application. The solid microneedles were subsequently coated with insulin-polymer films, using a 2D inkjet printing technology. The coating process achieved spatial control of the drug deposition, with quantitative accuracy. The microneedle geometry was shown to influence the morphology of the coating film, an effect that was pronounced during in the in vitro delivery studies of insulin to porcine skin. Furthermore, hollow microneedles were designed and 3D printed, featuring different heights. Two photopolymerisation-based technologies were studied, and their performance was compared. The key influential parameters of the printing outcome and microneedle quality were identified to be the printing angle and the size of the microneedle opening. The hollow microneedles were found to be effective in piercing porcine skin without structural damaging. The hollow microneedles were incorporated into complex patches with internal microfluidic structures for the provision and distribution of drug-containing solutions. The developed complex hollow microneedle patches were coupled with a microelectromechanical system to create a novel platform device for controlled, personalised transdermal drug delivery. Advanced imaging techniques revealed that the device achieved distribution of the liquid within porcine skin tissue without the creation of depots that would delay absorption. The device was evaluated for its efficacy to transdermally deliver a model dye and insulin in vitro. In vivo trials were also conducted using diabetic rodents, with the device achieving faster onset of insulin action and sustained glycemic control, in comparison to subcutaneous injections. Overall, the findings of the present research are anticipated to elucidate key problematic areas associated with the application of 3D printing for microneedle manufacturing and propose feasible solutions. The outermost goal of this work is to contribute to the advancement of knowledge in the field of 3D printed transdermal drug delivery systems, in order to bring them one step closer to their adoption in the clinical setting.