Fabrication of 3D Printed Hollow Microneedles by Digital Light Processing for the Buccal Delivery of Actives
Paraskevi Kyriaki Monou, Eleftherios G. Andriotis, Konstantinos Tsongas, Emmanouil K. Tzimtzimis, Orestis L. Katsamenis, Dimitrios Tzetzis, Pinelopi Anastasiadou, Christos Ritzoulis, Ioannis S. Vizirianakis, Dimitrios Andreadis, Dimitrios G. Fatouros
Abstract
In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device. Light microscopy was used to quality control the printability of the designs, confirming that the actual dimensions are in agreement with the digital design. Non-destructive volume imaging by means of microfocus computed tomography was employed for dimensional and defect characterization of the DLP-printed devices, demonstrating the actual volumes of the reservoirs and the malformations that occurred during printing. The penetration test and finite element analysis showed that the maximum stress experienced by the needles during the insertion process (10 N) was below their ultimate compressive strength (240-310 N). Permeation studies showed the increased permeability of three model drugs when delivered with the MN devices. Size-exclusion chromatography validated the stability of all the actives throughout the permeability tests. The safety of these printed devices for buccal administration was confirmed by histological evaluation and cell viability studies using the TR146 cell line, which indicated no toxic effects.