Evaluation of 3D-printed microneedles for potential use in the treatment of depression
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0000-0002-2672-6171 Date
2026-03-26
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APGI, APV and SITELF (Association de Pharmacie Galénique Industrielle / International Society of Drug Delivery Sciences and Technology; Arbeitsgemeinschaft für Pharmazeutische Verfahrenstechnik e. V. / International Association for Pharmaceutical Technology and Industrial Pharmacy; SITELF Italian Association of Pharmaceutical Technology and Legislation)
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Abstract
INTRODUCTION Agomelatine is an antidepressant used to treat major depressive episodes in adults. Currently, it is only available on the market as an oral tablet, but its bioavailability after oral administration is less than 5% [1] due to the extensive liver metabolism. Finding an alternative route of administration for this substance can result in an increased bioavailability and smaller doses of the drug necessary to achieve a therapeutic effect, which in turn translates into a reduced risk of side effects and more effective therapy. This study aimed to develop microneedles as a delivery system for transdermal administration of agomelatine. The use of microneedle systems is intended to overcome the stratum corneum barrier and facilitate the penetration of the drug into the dermis, from where it can be absorbed into the bloodstream. Microneedles were manufactured using 3D-printing, which is being intensively researched for medical applications and ensures fast and efficient production of systems, and the possibility of personalizing the devices. Two 3D-printing techniques: PolyJet and Masked Stereolithography were used. Agomelatine was introduced into the systems directly and in the form of a coating from a previously prepared gel. The microneedles were subjected to permeation test on human skin ex vivo, penetration test, and were also examined for stability and toxicity to determine the most suitable type for in vivo studies. MATERIALS AND METHODS Microneedle systems were manufactured in a 3D-printing process, using PolyJet method and Masked Stereolithography (MSLA) method, both of which involve curing photosensitive resin with UV light. The initial design of microneedle systems differed in shape, length, and the number of needles on the base. Microneedles manufacturing and coating Microneedle systems were printed using Sonic Mini 8K Phrozen (Hsinchu, Taiwan) printer for MSLA method, and Stratasys J5 (Stratasys Ltd., Eden Prairie, MN, USA) for PolyJet method. In both cases, biocompatible printing material was used. Initially, four geometries of microneedles were printed (cones, pyramids, rockets, and spearheads). Two methods of drug loading were applied. The first involved adding the drug dissolved in ethanol to the resin before printing. The second was coating with the gel containing agomelatine, either dissolved in ethanol or in the form of a suspension. Ex vivo permeation study Permeation studies were performed using full-thickness human skin (Biopredic International, France) and Franz diffusion cells (Teledyne Hanson Research, USA). Samples of the skin with microneedles were mounted on Franz diffusion cells filled with Phosphate Buffered Saline (PBS) pH=7,4 with the addition of sodium azide (0,02% w/v). The study was conducted over 7 days. Samples of acceptor fluid were taken at specified time points and replaced with a fresh medium. The samples were analyzed using High Performance Liquid Chromatography (Shimadzu, Nexera, Japan). Insertion study Insertion test was performed with the use of a Shimadzu AGS-X texture analyzer (Shimadzu, Kyoto, Japan) and TrapeziumX 1.52 software (Shimadzu, Japan). The microneedle system was mounted on the cylindrical sensor placed above 10 layers of laboratory Parafilm® (1270 µm), situated on a metal table. The sensor moved downward at 0.05 mm/s until the force of 32 N [2], and then was held in place for 30 seconds. The number of holes in each layer of Parafilm® M was calculated. Additionally, for Pyramid geometry, microneedles were inserted into a full-thickness human skin sample. Then, the sample was frozen at -80°C, cut using the cryomicrotome (Leica Microsystems, CM1850-1-1, Nussloch, Germany), and investigated under a microscope to confirm the epidermis disruption. Stability studies The stability and photostability of the prepared samples were determined using a temperature and humidity chamber with illumination, TH-ICH-800 (Jeio Tech Co., Ltd., Daejeon, Republic of Korea), according to the ICH guidelines Q1A and Q1B. Microtox acute toxicity study The toxicity of the microneedles was evaluated following the procedure of the 81.9% Screening test with slight modifications [3]. Microtox acute reagent (lyophilized Aliivibrio fischeri bacteria; ModernWater plc, London, United Kingdom) was rehydrated, diluted tenfold with Microtox Diluent, and incubated at 15°C for 15 minutes. Then the bioluminescence of the Aliivibrio fischeri bacterial suspension was measured, and the microneedle system sample was added. Changes in bioluminescence were measured after 5 and 15 minutes. RESULTS Both printing methods proved effective in obtaining good resolution of microneedles with different geometries, but only the MSLA method allowed the drug to be introduced into the matrix by adding it to the resin before printing. In contrast, both methods were successful in applying agomelatine to the microneedle systems by coating [Figure 1]. Figure 1. Microneedle coating process utilizing dedicated tooling. The permeation study showed that the drug passes into the acceptor fluid from all tested formulations, which indicates effective skin barrier penetration. In addition, microneedle systems containing agomelatine incorporated into the system matrix (“MIX” type) showed a nearly linear relationship between the amount of drug released and time. Considering the MSLA method, the rocket geometry was prone to breakage, and the Spearhead geometry required more force to penetrate than the cones, despite having the same number of needles per base. Pyramid geometry, which performed worst in the test using Parafilm®, was additionally tested on a sample of full-thickness human skin [Figure 2], and proved its efficiency. Of the two methods, PolyJet microneedles proved to be more effective at penetrating Parafilm®. Figure 2. The photo of skin cross-section with visible holes in the epidermis of the human skin sample. Stability studies indicated a decrease in the amount of agomelatine in most samples at temperature 40±2°C and 75±5% humidity over a period of up to 3 months. However, no clear influence of geometry or gel type on photostability was found. MSLA method showed lower toxicity than PolyJet in some cases, and drug loading did not cause an increase in the toxic effect in this method. CONCLUSIONS Both printing methods proved to be accurate, but only MSLA allowed the drug to be loaded directly into the system matrix. Moreover, the need for packaging that protects against external factors was demonstrated. Penetration tests allowed Pyramids and cones to be selected as the most promising geometries for further research. Also, for MSLA systems, AGM did not increase the toxicity of the samples in the Microtox® test. REFERENCES B. Green, Focus on agomelatine, Current Medical Research and Opinion 27 (2011) 745–749. J. Leanpolchareanchai, N. Nuchtavorn, Response Surface Methodology for Optimization of Hydrogel-Forming Microneedles as Rapid and Efficient Transdermal Microsampling Tools, Gels 9 (2023) 306. B. Czarczynska-Goslinska, T. Goslinski, A. Roszak, A. Froelich, P. Szyk, D.T. Mlynarczyk, L. Sobotta, I. Budnik, O. Kordyl, T. Osmałek, Microneedle System Coated with Hydrogels Containing Protoporphyrin IX for Potential Application in Pharmaceutical Technology, MPs 7 (2024) 73.
Description
This repository contains a conference abstract entitled “Evaluation of 3D-printed microneedles for potential use in the treatment of depression”, submitted for the 15th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology, held on 23–26 March 2026 in Prague, Czech Republic. The meeting is an international scientific conference focused on pharmaceutics, biopharmaceutics and pharmaceutical technology.
The abstract describes studies on 3D-printed microneedle systems containing agomelatine, designed as potential transdermal drug delivery systems for the treatment of depression. The work focused on the fabrication and evaluation of microneedle systems produced using PolyJet and Masked Stereolithography 3D-printing techniques. Agomelatine was introduced either directly into the printed matrix or as a coating prepared from previously developed agomelatine-containing gels. The systems were evaluated using ex vivo permeation testing on human skin, insertion testing, stability and photostability studies, and Microtox acute toxicity testing.
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Wojtyłko M, Froelich A, Jadach B, Kuczko W, Wichniarek R, Mlynarczyk DT, Budna-Tukan J, Białek A, Osmałek T, Lamprou DA. Evaluation of 3D-printed microneedles for potential use in the treatment of depression. 15th World Meeting on Pharmaceutics, Biopharmaceutics and Pharmaceutical Technology; 23–26 March 2026; Prague, Czech Republic.