OPTIMIZATION OF GEOMETRY AND BUILDING ORIENTATION ON THE ACCURACY OF DISSOLVING MICRONEEDLE MASTERS USING STEREOLITHOGRAPHY
Abstract
Microneedles have gained prominence as a minimally invasive transdermal drug delivery technology, offering significant advantages such as reduced pain, targeted drug delivery, and decreased medical waste. This study focuses on the optimization of dissolvable self-locking microneedles fabricated using stereolithography (SLA), with an emphasis on dimensional accuracy. Three microneedle geometries—perpendicular, concave, and convex—were investigated across three building orientations (0°, 45°, and 60°). Microneedle masters were printed using SLA and subsequently used as molds to fabricate PDMS microneedle molds. Dimensional accuracy was evaluated based on errors in height, base, and angle, with optimization conducted using the Taguchi method. The results revealed that for microneedle masters, the perpendicular geometry paired with a 45° building orientation demonstrated the best accuracy, as confirmed by S/N ratio analysis and ANOVA. For microneedle molds, perpendicular geometry remained optimal, with the 60° orientation offering reduced errors due to improved stability during the demolding process. Morphological comparisons indicated notable differences between master and mold accuracy, attributed to stresses during demolding. This study underscores the critical role of geometry and building orientation in optimizing microneedle fabrication and highlights the effectiveness of the Taguchi method in reducing dimensional errors.
References
Kolli, C. S. (2015). Microneedles: Bench to Bedside. Therapeutic Delivery, 6(10), 1081–1088. https://doi.org/10.4155/tde.15.67
Feng, Y. H., Liu, J. L., Zhu, D. D., Hao, Y. Y., Guo, X. D. (2020). Multiscale simulations of drug distributions in polymer dissolvable microneedles. Colloids and Surfaces B: Biointerfaces, 189, 110844. https://doi.org/10.1016/j.colsurfb.2020.110844
Herwadkar, A., Banga, A. K. (2012). An update on the application of physical technologies to enhance intradermal and transdermal drug delivery. Therapeutic Delivery, 3(3), 339–355. https://doi.org/10.4155/tde.12.1
Accurso, V., Winnicki, M., Shamsuzzaman, S. M. A., Wenzel, A., Johnson, K. A., Somers, V. K. (2001). Predisposition to vasovagal syncope in subjects with blood/injury phobia. Circulation. http://www.circulationaha.org
Waghule, T., Singhvi, G., Dubey, S. K., Pandey, M. M., Gupta, G., Singh, M., Dua, K. (2019). Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomedicine & Pharmacotherapy, 109, 1249–1258. https://doi.org/10.1016/j.biopha.2018.10.078
Alsbrooks, K., Hoerauf, K. (2022). Prevalence, causes, impacts, and management of needle phobia: An international survey of a general adult population. PLoS One, 17(10), e0276814. https://doi.org/10.1371/journal.pone.0276814
Luzuriaga, M. A., Berry, D. R., Reagan, J. C., Smaldone, R. A., Gassensmith, J. J. (2018). Biodegradable 3D printed polymer microneedles for transdermal drug delivery. Lab on a Chip, 18(8), 1223–1230. https://doi.org/10.1039/c8lc00098k
Gupta, J., Denson, D. D., Felner, E. I., Prausnitz, M. R. (2012). Rapid local anesthesia in humans using minimally invasive microneedles. Clinical Journal of Pain, 28(2), 129–135. https://doi.org/10.1097/AJP.0b013e318225dbe9.
Gupta, J., Park, S. S., Bondy, B., Felner, E. I., Prausnitz, M. R. (2011). Infusion pressure and pain during microneedle injection into skin of human subjects. Biomaterials, 32(28), 6823–6831. https://doi.org/10.1016/j.biomaterials.2011.05.061.
Cleary, G. W. (2011). Microneedles for drug delivery. Pharmaceutical Research, 28(1), 1–6. https://doi.org/10.1007/s11095-010-0307-3.
Bhattacharjee, G., Gohil, N., Shukla, M., Sharma, S., Mani, I., Pandya, A., Chu, D. T., Le Bui, N., Thi, Y. V. N., Khambhati, K., Maurya, R., Ramakrishna, S., Singh, V. (2023). Exploring the potential of microfluidics for next-generation drug delivery systems. OpenNano, 12, 100150. https://doi.org/10.1016/j.onano.2023.100150.
Nagarkar, R., Singh, M., Nguyen, H. X., Jonnalagadda, S. (2020). A review of recent advances in microneedle technology for transdermal drug delivery. Journal of Drug Delivery Science and Technology, 59, 101923. https://doi.org/10.1016/j.jddst.2020.101923.
C Yeung, C., Chen, S., King, B., Lin, H., King, K., Akhtar, F., Diaz, G., Wang, B., Zhu, J., Sun, W., Khademhosseini, A., Emaminejad, S. (2019). A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery. Biomicrofluidics, 13(6), 064125. https://doi.org/10.1063/1.5127778.
Mutlu, M. E., Akdag, Z., Pilavci, E., Ulag, S., Daglilar, S., Gunduz, O. (2025). Production of microneedle patches coated with polyvinyl-alcohol/sucrose/gentamicin sulfate for skin treatment. Materials Letters, 378, 137557. https://doi.org/10.1016/j.matlet.2024.137557.
Krieger, K. J., Bertollo, N., Dangol, M., Sheridan, J. T., Lowery, M. M., O’Cearbhaill, E. D. (2019). Simple and customizable method for fabrication of high-aspect ratio microneedle molds using low-cost 3D printing. Microsystems & Nanoengineering, 5, 42. https://doi.org/10.1038/s41378-019-0088-8.
Ito, Y., Yoshimitsu, J.-I., Shiroyama, K., Sugioka, N., Takada, K. (2006). Self-dissolving microneedles for the percutaneous absorption of EPO in mice. Journal of Drug Targeting, 14(4), 255–261. https://doi.org/10.1080/10611860600785080.
Yuan, W., Hong, X., Wu, Z., Chen, L., Liu, Z., Wu, F., Wei, L. (2013). Dissolving and biodegradable microneedle technologies for transdermal sustained delivery of drug and vaccine. Drug Design, Development and Therapy, 7, 945–952. https://doi.org/10.2147/DDDT.S44401.
Tuan-Mahmood, T. M., McCrudden, M. T. C., Torrisi, B. M., McAlister, E., Garland, M. J., Singh, T. R. R., Donnelly, R. F. (2013). Microneedles for intradermal and transdermal drug delivery. European Journal of Pharmaceutical Sciences, 50(5), 623–637. https://doi.org/10.1016/j.ejps.2013.05.005.
Pham, H. P., Vo, V. T., Nguyen, T. Q. (2024). Optimizing CNC milling parameters for manufacturing of ultra-sharp tip microneedle with various tip angles. Drug Delivery and Translational Research. https://doi.org/10.1007/s13346-024-01740-5.
Wang, X., Shujaat, S., Shaheen, E., Jacobs, R. (2021). Accuracy of desktop versus professional 3D printers for maxillofacial model production: A systematic review and meta-analysis. Journal of Dentistry, 112, 103741. https://doi.org/10.1016/j.jdent.2021.103741.
Evens, T., Malek, O., Castagne, S., Seveno, D., Van Bael, A. (2020). A novel method for producing solid polymer microneedles using laser ablated moulds in an injection moulding process. Manufacturing Letters, 24, 29–32. https://doi.org/10.1016/j.mfglet.2020.03.009.
Bolton, C. J. W., Howells, O., Blayney, G. J., Eng, P. F., Birchall, J. C., Gualeni, B., Roberts, K., Ashraf, H., Guy, O. J. (2020). Hollow silicon microneedle fabrication using advanced plasma etch technologies for applications in transdermal drug delivery. Lab on a Chip, 20(15), 2788–2795. https://doi.org/10.1039/D0LC00567C.
Xenikakis, I., Tzimtzimis, M., Tsongas, K., Andreadis, D., Demiri, E., Tzetzis, D., Fatouros, D. G. (2019). Fabrication and finite element analysis of stereolithographic 3D printed microneedles for transdermal delivery of model dyes across human skin in vitro. European Journal of Pharmaceutical Sciences, 137, 104976. https://doi.org/10.1016/j.ejps.2019.104976.
Yang, Q., Zhong, W., Liu, Y., Hou, R., Wu, Y., Yan, Q., Yang, G. (2023). 3D-printed morphology-customized microneedles: Understanding the correlation between their morphologies and the received qualities. International Journal of Pharmaceutics, 638, 122873. https://doi.org/10.1016/j.ijpharm.2023.122873.
Choo, S., Jin, S., Jung, J. (2022). Fabricating high-resolution and high-dimensional microneedle mold through the resolution improvement of stereolithography 3D printing. Pharmaceutics, 14(4), 766. https://doi.org/10.3390/pharmaceutics14040766.
Unkovskiy, A., Bui, P. H. B., Schille, C., Geis-Gerstorfer, J., Huettig, F., Spintzyk, S. (2018). Objects build orientation, positioning, and curing influence dimensional accuracy and flexural properties of stereolithographically printed resin. Dental Materials, 34(12), e324–e333. https://doi.org/10.1016/j.dental.2018.09.011.
Chanabodeechalermrung, B., Chaiwarit, T., Udomsom, S., Rachtanapun, P., Piboon, P., Jantrawut, P. (2024). Determination of vat-photopolymerization parameters for microneedles fabrication and characterization of HPMC/PVP K90 dissolving microneedles utilizing 3D-printed mold. Scientific Reports, 14, 11078. https://doi.org/10.1038/s41598-024-67243-y.
Johnson, A. R., Procopio, A. T. (2019). Low-cost additive manufacturing of microneedle masters. 3D Printing in Medicine, 5, 3. https://doi.org/10.1186/s41205-019-0039-x.
Joo, S. H., Kim, J., Hong, J., Fakhraei Lahiji, S., Kim, Y. H. (2023). Dissolvable self-locking microneedle patches integrated with immunomodulators for cancer immunotherapy. Advanced Materials, 35(20), 2209966. https://doi.org/10.1002/adma.202209966.
Balmert, S. C., Carey, C. D., Falo, G. D., Sethi, S. K., Erdos, G., Korkmaz, E., Falo, L. D. (2020). Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination. Journal of Controlled Release, 317, 336–346. https://doi.org/10.1016/j.jconrel.2019.11.023.
Hamzaçebi, C. (2021). Taguchi Method as a Robust Design Tool. In Quality Control - Intelligent Manufacturing, Robust Design and Charts. IntechOpen. https://doi.org/10.5772/intechopen.94908.
Fitaihi, R., Abukhamees, S., Chung, S. H., Craig, D. Q. M. (2024). Optimization of stereolithography 3D printing of microneedle micro-molds for ocular drug delivery. International Journal of Pharmaceutics, 658, 124195. https://doi.org/10.1016/j.ijpharm.2024.124195.
IEEE. (2014). Control Automation Robotics & Vision (ICARCV), 2014 13th International Conference on: 10–12 Dec. 2014. IEEE. https://ieeexplore.ieee.org/document/7064393.
