Applied Chemistry for Engineering (공업화학)

The Korean Society of Industrial and Engineering Chemistry (한국공업화학회)
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Comparison and Evaluation of Printing Angle Dependent Fabrication of Microneedles Using Polyjet and DLP-SLA 3D Printers

Polyjet과 DLP-SLA 3D 프린터를 이용한 인쇄 각도에 따른 마이크로니들 제작의 비교 및 평가

  • Seung Hui An (Department of Chemical and Biomolecular Engineering, Chonnam National University) ;
  • Heon-Ho Jeong (Department of Chemical and Biomolecular Engineering, Chonnam National University)
  • 안승희 (전남대학교 화공생명공학과) ;
  • 정헌호 (전남대학교 화공생명공학과)
  • Received : 2024.08.12
  • Accepted : 2024.09.21
  • Published : 2024.10.10
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Abstract

Microneedles with micron-sized needle arrays are an emerging technology for the transdermal administration of active pharmaceutical ingredients with minimally invasive pain. Over the past decade, although various additive manufacturing technologies have been employed for precise fabrication of microneedles, these methods are often limited by material compatibility and bioavailability, in addition to being time-consuming and costly. In here, we compare the resolution of Polyjet and DLP-SLA 3D printing methods for the precise fabrication of biodegradable PCLDA/PEGDA microneedles. To enhance the structural accuracy of the microneedles from both printing methods, we evaluate the 3D printing conditions, including 3D printing angle and needle height and diameter. Molds for microneedles are fabricated using optimized 3D printing methods, and subsequent replica molding processes are employed to fabricate the polymeric microneedles with sharp need tips. Finally, we use photocurable PCLDA and PEGDA for biodegradable and biocompatible microneedles, and their mechanical properties as PCLDA concentrations are analyzed to assess the strength required for skin insertion. This study has demonstrated the efficient and low-cost fabrication of high-resolution microneedles for transdermal drug delivery.

마이크론 크기의 미세바늘 배열로 구성된 마이크로니들은 최소 침습성 통증으로 활성 의약품 성분을 경피 투여하기 위한 새로운 기술이다. 지난 수년간 마이크로니들의 구조를 정확히 제조하기 위해 다양한 적층 제조 기술이 사용되었지만 기존의 기술은 시간과 비용이 많이 드는 것뿐만 아니라 제한적인 재료 호환성과 생체 이용률에 대한 한계성이 있었다. 본 연구에서는 생분해성 PCLDA/PEGDA 마이크로니들의 정확한 제조를 위해 Polyjet과 DLP-SLA 3D 프린팅 방법의 해상도를 비교하였다. 두 3D 프린팅 방식을 기반으로 마이크로니들의 구조적 정확성을 향상시키기 위해 3D 프린팅 각도, 바늘 높이 및 직경을 포함한 3D 프린팅 조건을 비교 및 평가하였다. 최적화된 3D 프린팅 조건을 적용하여 날카로운 바늘 끝을 가진 마이크로니들 몰드를 제작하였으며, 복제 성형 공정을 통해 고분자 마이크로니들을 제작하였다. 최종적으로, 광경화성 PCLDA와 PEGDA를 이용한 생분해성/생체적합성 마이크로니들을 제작하였으며, PCLDA 농도에 따른 기계적 특성 제어를 통해 피부 삽입에 필요한 강도를 평가하였다. 본 연구에서는 3D 프린팅을 이용해 고해상도 마이크로니들을 저비용 및 효율적으로 제작하여 경피 약물 전달 분야에 응용할 수 있음을 증명하였다.

Keywords

References

  1. S. P. Sullivan, D. G. Koutsonanos, M. del Pilar Martin, J .W. Lee, V. Zarnitsyn, S.-O. Choi, N. Murthy, R. W. Compans, I. Skountzou, and M. R. Prausnitz, Dissolving polymer microneedle patches for influenza vaccination, Nat. Med., 16, 915-920 (2010). 
  2. M.-H. Ling and M.-C. Chen, Dissolving polymer microneedle patches for rapid and efficient transdermal delivery of insulin to diabetic rats, Acta Biomater., 9, 8952-8961 (2013). 
  3. B. Chua, S. P. Desai, M. J. Tierney, J. A. Tamada, and A. N. Jina, Effect of microneedles shape on skin penetration and minimally invasive continuous glucose monitoring in vivo, Sens. Actuators A: Phys., 203, 373-381 (2013). 
  4. Z. Xiang, J. Liu, and C. Lee, A flexible three-dimensional electrode mesh: An enabling technology for wireless brain-computer interface prostheses, Microsyst. Nanoeng., 2, 1-8 (2016). 
  5. A. V. Romanyuk, V. N. Zvezdin, P. Samant, M. I. Grenader, M. Zemlyanova, and M. R. Prausnitz, Collection of analytes from microneedle patches, Anal. Chem., 86, 10520-10523 (2014). 
  6. M. Kim, T. Kim, D. S. Kim, and W. K. Chung, Curved microneedle array-based sEMG electrode for robust long-term measurements and high selectivity, Sensors, 15, 16265-16280 (2015). 
  7. G. S. Guvanasen, L. Guo, R. J. Aguilar, A. L. Cheek, C. S. Shafor, S. Rajaraman, T. R. Nichols, and S. P. DeWeerth, A stretchable microneedle electrode array for stimulating and measuring intramuscular electromyographic activity, IEEE Trans. Neural Syst. Rehabil. Eng., 25, 1440-1452 (2016). 
  8. G. Stavrinidis, K. Michelakis, V. Kontomitrou, G. Giannakakis, M. Sevrisarianos, G. Sevrisarianos, N. Chaniotakis, Y. Alifragis, and G. Konstantinidis, SU-8 microneedles based dry electrodes for Electroencephalogram, Microelectron. Eng., 159, 114-120 (2016). 
  9. M. Tezuka, K. Ishimaru, and N. Miki, Electrotactile display composed of two-dimensionally and densely distributed microneedle electrodes, Sens. Actuators A: Phys., 258, 32-38 (2017). 
  10. S. Pradeep Narayanan and S. Raghavan, Fabrication and characterization of gold-coated solid silicon microneedles with improved biocompatibility, Int. J. Adv. Manuf. Tech., 104, 3327-3333 (2019). 
  11. F. S. Iliescu, J. C. M. Teo, D. Vrtacnik, H. Taylor, and C. Iliescu, Cell therapy using an array of ultrathin hollow microneedles, Microsyst. Technol., 24, 2905-2912 (2018). 
  12. M. A. Boks, W. W. Unger, S. Engels, M. Ambrosini, Y. van Kooyk, and R. Luttge, Controlled release of a model vaccine by nanoporous ceramic microneedle arrays, Int. J. Pharm., 491, 375-383 (2015). 
  13. S. Lee, S. Fakhraei Lahiji, J. Jang, M. Jang, and H. Jung, Micropillar integrated dissolving microneedles for enhanced transdermal drug delivery, Pharmaceutics, 11, 402 (2019). 
  14. O. Khandan, M. Y. Kahook, and M. P. Rao, Fenestrated microneedles for ocular drug delivery, Sens. Actuators B: Chem., 223, 15-23 (2016). 
  15. S. Li, S. Dong, W. Xu, S. Tu, L. Yan, C. Zhao, J. Ding, and X. Chen, Antibacterial hydrogels, Adv. Sci., 5, 1700527 (2018). 
  16. N. Wilke, A. Mulcahy, S.-R. Ye, and A. Morrissey, Process optimization and characterization of silicon microneedles fabricated by wet etch technology, Microelectron. J., 36, 650-656 (2005). 
  17. H. Takahashi, Y. J. Heo, N. Arakawa, T. Kan, K. Matsumoto, R. Kawano, and I. Shimoyama, Scalable fabrication of microneedle arrays via spatially controlled UV exposure, Microsyst. Nanoeng., 2, 1-9 (2016). 
  18. N. Roxhed, P. Griss, and G. Stemme, A method for tapered deep reactive ion etching using a modified Bosch process, J. Micromech. Microeng., 17, 1087 (2007). 
  19. T. Omatsu, K. Chujo, K. Miyamoto, M. Okida, K. Nakamura, N. Aoki, and R. Morita, Metal microneedle fabrication using twisted light with spin, Opt. Express, 18, 17967-17973 (2010). 
  20. B. Bediz, E. Korkmaz, R. Khilwani, C. Donahue, G. Erdos, L. D. Falo, and O. B. Ozdoganlar, Dissolvable microneedle arrays for intradermal delivery of biologics: fabrication and application, Pharm. Res., 31, 117-135 (2014). 
  21. H. Jansen, M. de Boer, R. Legtenberg, and M. Elwenspoek, The black silicon method: a universal method for determining the parameter setting of a fluorine-based reactive ion etcher in deep silicon trench etching with profile control, J. Micromech. Microeng., 5, 115 (1995). 
  22. P. P. T. Nguyen, S. An, and H.-H. Jeong, Microfluidic formation of biodegradable PCLDA microparticles as sustainable sorbents for treatment of organic contaminants in wastewater, Colloids Surf. A: Physicochem. Eng. Asp., 656, 130409 (2023). 
  23. E. Larraneta, J. Moore, E. M. Vicente-Perez, P. Gonzalez-Vazquez, R. Lutton, A. D. Woolfson, and R. F. Donnelly, A proposed model membrane and test method for microneedle insertion studies, Int. J. Pharm., 472, 65-73 (2014). 
  24. K. Cheung, T. Han, and D. B. Das,, Effect of force of microneedle insertion on the permeability of insulin in skin, J. Diabetes Sci. Technol., 8, 444-452 (2014).