Transdermal delivery of insulin across human skin in vitro with 3D printed hollow microneedles

January 24, 2022

Iakovos Xenikakis (1), Konstantinos Tsongas (2), Emmanouil K. Tzimtzimis (2), Orestis L. Katsamenis (3), Efterpi Demiri (4), Constantinos K. Zacharis (5), Despoina Georgiou (6), Eleni P. Kalogianni (6), Dimitrios Tzetzis (2), Dimitrios G. Fatouros (1)
Journal of Drug Delivery Science and Technology. Volume 67 (January 2022). DOI:


3D printed hollow microneedles, insulin, transdermal delivery


In the current study hollow microneedles (HMNs) were fabricated by means of vat polymerization method for the transdermal delivery of insulin. Two geometries of HMNs were designed in a Computer Aided Design (CAD) software namely, curved pyramid and syringe-like and fabricated with Liquid Crystal Display (LCD) method. Dimensions were determined and quality features were imaged with scanning electron microscopy (SEM). Volumetric characterization of HMNs and microchannels was performed by microfocus computed tomography (μCT) whereas mechanical characterization and skin penetration tests of the two geometries were carried out both experimentally and by Finite Element Analysis (FEA) simulation. Diffusion studies of insulin across full thickness human skin were performed in vitro using Franz diffusion cells. Insulin samples were analyzed with liquid chromatography-mass spectrometry (LC-MS). The results show that the transport might be affected by the shape of the microneedles.

How Our Software Was Used

Volume segmentation and quantification was conducted in Dragonfly. For the analysis each volume was “split” in two along the Z-axis, resulting into two sub-volumes: one containing the protruding needles and the other one their lumen. Following thresholding-based segmentation, each needle and each lumen was analyzed independently and the following measured were calculated: Volume (mm³), Volume/Surface Area (mm), Maximum Location Z (mm) - Maximum Location Z (mm), Aspect Ratio and Minimum Feret Diameter (mm).

Author Affiliation

(1) Department of Pharmacy, Division of Pharmaceutical Technology, Aristotle University of Thessaloniki, Thessaloniki, 54124, Greece
(2) Digital Manufacturing and Materials Characterization Laboratory, School of Science and Technology, International Hellenic University, 14km Thessaloniki - N. Moudania, Thermi, GR57001, Greece
(3) μ-VIS X-Ray Imaging Centre, Faculty of Engineering and Physical Sciences, University of Southampton, SO17 1BJ, Southampton, UK
(4) Department of Plastic Surgery, Medical School, Papageorgiou Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece
(5) Laboratory of Pharmaceutical Analysis, Department of Pharmaceutical Technology, School of Pharmacy, Aristotle University of Thessaloniki, GR-54124, Greece
(6) Department of Food Science and Technology, International Hellenic University, Sindos Campus, 57400, Thessaloniki, Greece