Applied Chemistry for Engineering (공업화학)

The Korean Society of Industrial and Engineering Chemistry (한국공업화학회)
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Recent Research Trend in Microneedle Fabrication Using 3D Printing

3D 프린팅을 이용한 마이크로니들 제작의 최신 연구 동향

  • Choo, Sangmin (Department of Pharmaceutical Engineering, Dankook University) ;
  • Jung, Jae Hwan (Department of Pharmaceutical Engineering, Dankook University)
  • 추상민 (단국대학교 생명공학대학 제약공학과) ;
  • 정재환 (단국대학교 생명공학대학 제약공학과)
  • Received : 2021.06.18
  • Accepted : 2021.07.05
  • Published : 2021.08.10
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Abstract

A microneedle is a tool that used for drug delivery and diagnosis. Unlike general injections, the microneedle is short in length, enabling effective drug delivery while minimizing pain and risk of infection. Conventionally, microneedles have been manufactured precisely at a nanometer level based on microelectro mechanical systems (MEMS) technology, requiring expensive equipments & maintenance and complicated processes. To address the issues, 3D printing research has been conducted to fabricate microneedles simply, economically, and rapidly. Since 3D printing facilitates to manufacture prototypes and apply feedbacks, it is advantageous for the development and commercialization of microneedle for pharmaceuticals and cosmetics. Therefore, this review will introduce stereolithography (SLA), two-photon polymerization (2PP), dynamic light processing (DLP), continuous liquid interface production (CLIP), and fused deposition modeling (FDM) 3D printing technologies and also highlight research trends for microneedle production using them. Furthermore, the limitation of the current microneedle technology and the direction to be solved in the future will be discussed.

마이크로니들은 약물전달 및 진단에 사용되는 미세바늘로 일반 주사와 달리 길이가 짧아 효과적으로 약물을 전달하는 한편 고통과 감염위험은 최소화시킬 수 있는 도구이다. 기존의 마이크로니들은 MEMS 기술을 기반으로 정밀하게 나노미터 수준으로 제작되었으나 장비와 유지비가 비싸고 공정이 복잡하여, 최근에는 3D 프린팅을 이용해 경제적이고 간단하며 신속하게 마이크로니들을 제작하는 연구가 진행 중이다. 3D 프린팅 기술은 프로토타입의 제작이 간단하고 수정 보완이 용이하기 때문에 마이크로니들 의약품 및 화장품의 상용화에 유리하다. 이에 본 총설은 SLA, 2PP, DLP, CLIP, FDM 3D 프린팅 기술에 대해 소개하고, 이를 이용한 마이크로니들 제작 연구동향에 대해 소개하고자 한다. 또한 현재 마이크로니들 기술의 한계점과 앞으로 해결해야 할 부분에 대해서 논해보고자 한다.

Keywords

Acknowledgement

본 연구는 단국대학교 제약공학과 소속 저자의 결과물로서 해당 학과는 2020년도 단국대학교 대학혁신지원사업 연구중심학과 육성사업지원을 받았음.

References

  1. Y. Kim, J. Park, and M. R. Prausnitz, Microneedles for drug and vaccine delivery, Adv. Drug Deliv. Rev., 64, 1547-1568 (2012). https://doi.org/10.1016/j.addr.2012.04.005
  2. H. S. Gill, J. Soderholm, M. R. Prausnitz, and M Sallberg., Cutaneous vaccination using microneedles coated with hepatitis C DNA vaccine. Gene Ther., 17, 811-814 (2010). https://doi.org/10.1038/gt.2010.22
  3. P. M. Wang, M. Cornwell, J. Hill, and M. R. Prausnitz, Precise Microinjection into Skin Using Hollow Microneedles, J. Invest. Dermatol., 126, 1080-1087 (2006). https://doi.org/10.1038/sj.jid.5700150
  4. J. Jung, and S. Jin, Microneedle for transdermal drug delivery: current trends and fabrication., Int. J. Pharm. Investig., 1-15 (2021).
  5. J. Lee, and M. R. Praunistz, Drug delivery using microneedle patches: not just for skin, Expert Opin. Drug Deliv., 15, 541-543 (2018). https://doi.org/10.1080/17425247.2018.1471059
  6. M. R. Praunistz, Engineering Microneedle Patches for Vaccination and Drug Delivery to Skin, Annu. Rev. Chem. Biomol. Eng., 8, 177-200 (2017). https://doi.org/10.1146/annurev-chembioeng-060816-101514
  7. 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). https://doi.org/10.1088/0960-1317/17/5/031
  8. S. N. Economidou, and D. Douroumis, 3D printing as a transformative tool for microneedle systems: Recent advances, manufacturing considerations and market potential., Adv. Drug Deliv. Rev., 173, 60-69 (2021). https://doi.org/10.1016/j.addr.2021.03.007
  9. E. Larraneta, R. E. M. Lutton, A. D. Woolfson, and R. F. Donnelly, Microneedle arrays as transdermal and intradermal drug delivery systems : Materials science, manufacture and commercial development, Mater. Sci. Eng. R Rep., 104, 1-32 (2016). https://doi.org/10.1016/j.mser.2016.03.001
  10. J. Halder, S. Gupta, R. Kumari, G. Das Gupta, and V. K. Rai, Microneedle array: applications, recent advances, and clinical pertinence in transdermal drug delivery, J. Pharm. Innov., 1-8 (2020)
  11. S. N. Economidou, D. A. Lamprou, and D. Douroumis, 3D printing applications for transdermal drug delivery, Int. J. Pharm., 544, 415-424 (2018). https://doi.org/10.1016/j.ijpharm.2018.01.031
  12. E. A. Allen, C. O'Mahony, M. Cronin, T. O'Mahony, A. C. Moore, and A. M. Crean, Dissolvable microneedle fabrication using piezoelectric dispensing technology, Int. J. Pharm., 500, 1-10 (2016). https://doi.org/10.1016/j.ijpharm.2015.12.052
  13. C. Liaw, M. Guvendiren, Current and emerging applications of 3D printing in medicine, Biofabrication, 9, 024102 (2017). https://doi.org/10.1088/1758-5090/aa7279
  14. R. K. Chen, Y. an Jin, J. Wensman, and A. Shih, Additive manufacturing of custom orthoses and prostheses-A review, Addit. Manuf., 12, 77-89 (2016).
  15. D. Nesic, S. Durual, L. Marger, M. Mekki, I. Sailer, and S. S. Scherrer, Could 3D printing be the future for oral soft tissue regeneration?, Bioprinting, 20, e00100 (2020). https://doi.org/10.1016/j.bprint.2020.e00100
  16. D. Han, R. S. Morde, S. Mariani, A. A. La Mattina, E. Vignali, C. Yang, G. Barillaro, and H. Lee, 4D Printing of a bioinspired microneedle array with backward-facing barbs for enhanced tissue adhesion. Adv. Funct. Mater., 30, 1909197 (2020) https://doi.org/10.1002/adfm.201909197
  17. Z. Chen, Y. Lin, W. Lee, L. Ren, B. Liu, L. Liang, Z. Wang, and L. Jiang, Additive Manufacturing of Honeybee-Inspired Microneedle for Easy Skin Insertion and Difficult Removal, ACS Appl. Mater. Interfaces., 10, 29338-29346 (2018). https://doi.org/10.1021/acsami.8b09563
  18. M. Ogundele, and H. K. Okafor, Transdermal drug delivery: Microneedles, their fabrication and current trends in delivery methods, J. Pharm. Res. Int., 18, 1-14 (2017).
  19. C. Schmidleithner, and D. M. Kalaskar, Stereolithography, In: D. Cvetkovic, 3D Printing, 1-22, IntechOpen, London, UK (2018)
  20. M. A. Luzuriaga, D. R. Berry, J. C. Reagan, R. A. Smaldone, and J. J. Gassensmith, Biodegradable 3D printed polymer microneedles for transdermal drug delivery, Lab Chip, 18, 1223-1230 (2018). https://doi.org/10.1039/C8LC00098K
  21. M. Wu, Y. Zhang, H. Huang, J. Li, H. Liu, Z. Guo, L. Xue, S. Liu, and Y. Lei, Assisted 3D printing of microneedle patches for minimally invasive glucose control in diabetes, Mater. Sci. Eng. C, 117, 111299 (2020). https://doi.org/10.1016/j.msec.2020.111299
  22. N. Elahpour, F. Pahlevanzadeh, M. Kharaziha, H. R. BakhsheshiRad, S. RamaKrishna, and F. Berto, 3D printed microneedles for transdermal drug delivery: A brief review of two decades. Int. J. Pharm., 597, 120301 (2021). https://doi.org/10.1016/j.ijpharm.2021.120301
  23. K. J. Krieger, N. Bertollo, M. Dangol, J. T. Sheridan, M. M. Lowery, and E. D. O'Cearbhaill, Simple and customizable method for fabrication of high-aspect ratio microneedle molds using low-cost 3D printing. Microsyst. Nanoeng., 5, 1-14 (2019). https://doi.org/10.1038/s41378-018-0040-3
  24. M. A. Lopez-Ramirez, F. Soto, C. Wang, R. Rueda, S. Shukla, C. Silva-Lopez, D. Kupor, D. A. McBride, J. K. Pokorski, A. Nourhani, N. F. Steinmetz, N. J. Shah, and J. Wang, Built-In Active Microneedle Patch with Enhanced Autonomous Drug Delivery, Adv. Mater., 32, 1905740 (2019). https://doi.org/10.1002/adma.201905740
  25. R. I. Amer, G. H. El-Osaily, R. O. Bakr, R. S. El Dine, and A. M. Fayez, Characterization and Pharmacological Evaluation of Anti-Cellulite Herbal Product(s) Encapsulated in 3D-Fabricated Polymeric Microneedles, Sci. Rep., 10, 1-16 (2020). https://doi.org/10.1038/s41598-019-56847-4
  26. C. P. P. Pere, S. N. Economidou, G. Lall, C. Ziraud, J. S. Boateng, B. D. Alexander, D. A. Lamprou, and D. Douroumis, 3D printed microneedles for insulin skin delivery, Int. J. Pharm., 544, 425-432 (2018). https://doi.org/10.1016/j.ijpharm.2018.03.031
  27. S. N. Economidou, C. P. P. Pere, A. Reid, M. J. Uddin, J. F. Windmill, D. A. Lamprou, and D. Douroumis, 3D printed microneedle patches using stereolithography (SLA) for intradermal insulin delivery, Mater. Sci. Eng. C, 102, 743-755 (2019). https://doi.org/10.1016/j.msec.2019.04.063
  28. C. Yeung, S. Chen, B. King, H. Lin, K. King, F. Akhtar, G. Diaz, B. Wang, J. Zhu, W. Sun, A. Khademhosseini, and S. Emaminejad, A 3D-printed microfluidic-enabled hollow microneedle architecture for transdermal drug delivery, Biomicrofluidics, 13, 064125 (2019). https://doi.org/10.1063/1.5127778
  29. S. N. Economidou, M. J. Uddin, M. J. Marques, D. Douroumis, W. T. Sow, H. Li, A. Reid, J. F. C. Windmill, and A. Podoleanu, A novel 3D printed hollow microneedle microelectromechanical system for controlled, personalized transdermal drug delivery, Addit. Manuf., 38, 101815 (2021).
  30. K. Takada, H. Sun, and S. Kawata, Improved spatial resolution and surface roughness in photopolymerization-based laser nanowriting, Appl. Phys. Lett., 86, 071122 (2005). https://doi.org/10.1063/1.1864249
  31. S. C. Balmert, C. D. Carey, G. D. Falo, S. K. Sethi, G. Erdos, E. Korkmaz, and L. D. Falo Jr, Dissolving undercut microneedle arrays for multicomponent cutaneous vaccination, J. Control. Release, 317, 336-346 (2020). https://doi.org/10.1016/j.jconrel.2019.11.023
  32. Z. F. Rad, R. E. Nordon, C. J. Anthony, L. Bilston, P. D. Prewett, J. Arns, C. H. Arns, L. Zhang, and G. J. Davies, High-fidelity replication of thermoplastic microneedles with open microfluidic channels, Microsyst. Nanoeng., 3, 1-11 (2017).
  33. A. S. Cordeiro, I. A. Tekko, M. H. Jomaa, L. Vora, E. McAlister, F. Volpe-Zanutto, M. Nethery, P. T. Baine, N. Mitchell, D. W. McNeill, and R. F. Donnelly, Two-Photon Polymerisation 3D Printing of Microneedle Array Templates with Versatile Designs: Application in the Development of Polymeric Drug Delivery Systems, Pharm. Res., 37, 1-15 (2020). https://doi.org/10.1007/s11095-019-2719-z
  34. C. Plamadeala, S. R. Gosain, F. Hischen, B. Buchroithner, S. Puthukodan, J. Jacak, A. Bocchino, D. Whelan, C. O'Mahony, W. Baumgartner, and J. Heitz, Bio-inspired microneedle design for efficient drug/vaccine coating, Biomed. Microdevices, 22, 1-9, (2020). https://doi.org/10.1007/s10544-019-0454-1
  35. A. R. Johnson, and A. T. Procopio, Low cost additive manufacturing of microneedle masters, 3D Print. Med., 5, 1-10 (2019). https://doi.org/10.1186/s41205-019-0038-y
  36. N. El-Sayed, L. Vaut, and M. Schneider, Customized fast-separable microneedles prepared with the aid of 3D printing for nanoparticle delivery, Eur. J. Pharm. Biopharm., 154, 166-174 (2020). https://doi.org/10.1016/j.ejpb.2020.07.005
  37. A. Kundu, P. Arnett, A. Bagde, N. Azim, E. Kouagou, M. Singh, and S. Rajaraman, DLP 3D Printed "Intelligent" Microneedle Array (iµNA) for Stimuli Responsive Release of Drugs and Its in Vitro and ex Vivo Characterization, J. Microelectromech. Syst., 29, 685- 691 (2020). https://doi.org/10.1109/JMEMS.2020.3003628
  38. W. Yao, D. Li, Y. Zhao, Z. Zhan, G. Jin, H. Liang, and R. Yang, 3D printed multi-functional hydrogel microneedles based on high-precision digital light processing, Micromachines, 11, 17 (2020).
  39. J. R. Tumbleston, D. Shirvanyants, N. Ermoshkin, R. Janusziewicz, A. R. Johnson, D. Kelly, K. Chen, R. Prinschmidt, J. P. Rolland, A. Ermoshkin, E. T. Samulski, and J. M. Desimone, Continuous liquid interface production of 3D objects, Science, 347, 1349-1352 (2015). https://doi.org/10.1126/science.aaa2397
  40. A. R. Johnson, C. L. Caudill, J. R. Tumbleston, C. J. Bloomquist, K. A. Moga, A. Ermoshkin, D. Shirvanyants, S. J. Mecham, J. C. Luff, and J. M. DeSimone, Single-step fabrication of computationally designed microneedles by continuous liquid interface production, PLoS One, 11, e0162518 (2016). https://doi.org/10.1371/journal.pone.0162518
  41. C. L. Caudill, J. L. Perry, S. Tian, J. C. Luft, J. M. DeSimone, Spatially controlled coating of continuous liquid interface production microneedles for transdermal protein delivery, J. Control. Release, 284, 122-132 (2018). https://doi.org/10.1016/j.jconrel.2018.05.042
  42. C. J. Bloomquist, M. B. Mecham, M. D. Paradzinsky, R. Janusziewicz, S. B. Warner, J. C. Luft, S, J. Mecham, A. Z. Wang, and J. M. DeSimone, Controlling release from 3D printed medical devices using CLIP and drug-loaded liquid resins, J. Control. Release, 278, 9-23 (2018). https://doi.org/10.1016/j.jconrel.2018.03.026
  43. E. George, P. Liacouras, F. J. Rybicki, and D. Mitsouras, Measuring and establishing the accuracy and reproducibility of 3D printed medical models, Radiographics, 37, 1424-1450 (2017). https://doi.org/10.1148/rg.2017160165
  44. R. Ali, P. Mehta, M. S. Arshad, I. Kucuk, M. W. Chang, and Z. Ahmad, Transdermal microneedles-a materials perspective, AAPS Pharmscitech, 21, 1-14 (2020). https://doi.org/10.1208/s12249-019-1542-5