AccScience Publishing / IJB / Volume 8 / Issue 2 / DOI: 10.18063/ijb.v8i2.553
RESEARCH ARTICLE

Fast Customization of Hollow Microneedle Patches for Insulin Delivery

Rong Li1 Xuan Liu1 Xin Yuan1 Shanshan Wu2 Li Li1 Xuebing Jiang1 Bo Li1 Xian Jiang3 Maling Gou1*
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1 State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, China
2 Department of Ophthalmology, West China Hospital, Sichuan University, Chengdu, 610041, China
3 Department of Dermatology, West China Hospital, Sichuan University, Chengdu 610041, China
Submitted: 24 January 2022 | Accepted: 8 March 2022 | Published: 8 March 2022
© 2022 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Abstract

Hollow microneedle patches (HMNPs) have great promise for efficient and precise transdermal drug delivery in a painless manner. Currently, the clinical application of HMNPs is restricted by its complex manufacturing processes. Here, we use a new three-dimensional (3D) printing technology, static optical projection lithography (SOPL), for the fast fabrication of HMNPs. In this technology, a light beam is modulated into a customized pattern by a digital micromirror device (DMD) and projected to induce the spatial polymerization of monomer solutions which is controlled by the distribution of the light intensity in the monomer solutions. After an annulus picture is inputted into the DMD via the computer, the microneedles with hollow-cone structure can be precisely printed in seconds. By designing the printing pictures, the personalized HMNPs can be fast customized, which can afford the scale-up preparation of personalized HMNPs. Meanwhile, the obtained hollow microneedles (HMNs) have smooth surface without layer-by-layer structure in the commonly 3D-printed products. After being equipped with a micro-syringe, the HMNPs can efficiently deliver insulin into the skin by injection, resulting in effective control of the blood glucose level in diabetic mice. This work demonstrates a SOPL-based 3D printing technology for fast customization of HMNPs with promising medical applications.

Keywords
Microneedle
Three-dimensional printing
Hollow microneedle patches
Fabrication
Drug delivery
References

1. Gao B, Guo M, Lyu K, et al., 2021, Intelligent Silk Fibroin Based Microneedle Dressing (i-SMD). Adv Funct Mater, 31:2006839. http://doi.org/10.1002/adfm.202006839

2. Li X, Huang X, Mo J, et al., 2021, A Fully Integrated Closed-Loop System Based on Mesoporous Microneedles-Iontophoresis for Diabetes Treatment. Adv Sci (Weinh), 8:e2100827. http://doi.org/10.1002/advs.202100827

3. Yao S, Wang Y, Chi J, et al., 2021, Porous MOF Microneedle Array Patch with Photothermal Responsive Nitric Oxide Delivery for Wound Healing. Adv Sci (Weinh), 9:e2103449. http://doi.org/10.1002/advs.202103449

4. Sadeqi A, Kiaee G, Zeng W, et al., 2022, Hard Polymeric Porous Microneedles on Stretchable Substrate for Transdermal Drug Delivery. Sci Rep, 12:1853. http://doi.org/10.1038/s41598-022-05912-6

5. Economidou SN, Uddin MJ, Marques MJ, et al., 2021, A Novel 3D Printed Hollow Microneedle Microelectromechanical System for Controlled, Personalized Transdermal Drug Delivery. Addit Manuf, 38:101815. http://doi.org/10.1016/j.addma.2020.101815

6. Mishra R, Maiti TK, Bhattacharyya TK, 2019, Feasibility Studies on Nafion Membrane Actuated Micropump Integrated With Hollow Microneedles for Insulin Delivery Device. J Microelectromech Syst, 28:987–96. http://doi.org/10.1109/Jmems.2019.2939189

7. Niu L, Chu LY, Burton SA, et al., 2019, Intradermal Delivery of Vaccine Nanoparticles Using Hollow Microneedle Array Generates Enhanced and Balanced Immune Response. J. Control Release, 294:268–78. http://doi.org/10.1016/j.jconrel.2018.12.026

8. van der Maaden K, Heuts J, Camps M, et al., 2018, Hollow Microneedle-mediated Micro-injections of a Liposomal HPV E743-63 Synthetic Long Peptide Vaccine for Efficient Induction of Cytotoxic and T-helper Responses. J Control Release, 269:347–54. http://doi.org/10.1016/j.jconrel.2017.11.035

9. Gupta J, Denson DD, Felner EI, et al., 2012, Rapid Local Anesthesia in Humans Using Minimally Invasive Microneedles. Clin J Pain, 28:129–35. http://doi.org/10.1097/AJP.0b013e318225dbe9

10. Dardano P, De Martino S, Battisti M, et al., 2021, One-Shot Fabrication of Polymeric Hollow Microneedles by Standard Photolithography. Polymers (Basel), 13:520. http://doi.org/10.3390/polym13040520

11. Wang PC, Wester BA, Rajaraman S, et al., 2009, Hollow Polymer Microneedle Array Fabricated by Photolithography Process Combined with Micromolding Technique. Annu Int Conf IEEE Eng Med Biol Soc, 2009:7026–9. http://doi.org/10.1109/IEMBS.2009.5333317

12. Bolton CJ, Howells O, Blayney GJ, et al., 2020, Hollow Silicon Microneedle Fabrication Using Advanced Plasma Etch Technologies for Applications in Transdermal Drug Delivery. Lab Chip, 20:2788–95. http://doi.org/10.1039/d0lc00567c

13. Li Y, Zhang H, Yang R, et al., 2019, Fabrication of Sharp Silicon Hollow Microneedles by Deep-reactive Ion Etching Towards Minimally Invasive Diagnostics. Microsyst Nanoeng, 5:41. http://doi.org/10.1038/s41378-019-0077-y

14. Trautmann A, Roth GL, Nujiqi B, et al., 2019, Towards a Versatile Point-of-care System Combining Femto second Laser Generated Microfluidic Channels and Direct Laser Written Microneedle Arrays. Microsyst Nanoeng, 5:6. http://doi.org/10.1038/s41378-019-0046-5

15. Carcamo-Martinez A, Mallon B, Dominguez-Robles J, et al., 2021, Hollow Microneedles: A Perspective in Biomedical Applications. Int J Pharm, 599:120455. http://doi.org/10.1016/j.ijpharm.2021.120455

16. Xenikakis I, Tsongas K, Tzimtzimis EK, et al., 2021, Fabrication of Hollow Microneedles Using Liquid Crystal Display (LCD) Vat Polymerization 3D Printing Technology for Transdermal Macromolecular Delivery. Int J Pharm, 597:120303. http://doi.org/10.1016/j.ijpharm.2021.120303

17. Yeung C, Chen S, King B, et al., 2019, A 3D-Printed Microfluidic-enabled Hollow Microneedle Architecture for Transdermal Drug Delivery. Biomicrofluidics, 13:064125. http://doi.org/10.1063/1.5127778

18. Ovsianikov BC, Mente P, Monteiro-Riviere NA, et al., 2007, Two Photon Polymerization of Polymer–Ceramic Hybrid Materials for Transdermal Drug Delivery. Int J Appl Ceram Technol, 4:22–9. http://doi.org/10.1111/j.1744-7402.2007.02115.x

19. Mathew E, Pitzanti G, Dos Santos AL, et al., 2021, Optimization of Printing Parameters for Digital Light Processing 3D Printing of Hollow Microneedle Arrays. Pharmaceutics, 13:1837. http://doi.org/10.3390/pharmaceutics13111837

20. Liao C, Anderson W, Antaw F, et al., 2019, Two-Photon Nanolithography of Tailored Hollow three-dimensional Microdevices for Biosystems. ACS Omega, 4:1401–9. http://doi.org/10.1021/acsomega.8b03164

21. Doraiswamy A, Ovsianikov A, Gittard SD, et al., 2010, Fabrication of Microneedles Using Two Photon Polymerization for Transdermal Delivery of Nanomaterials. J Nanosci Nanotechnol, 10:6305–12. http://doi.org/10.1166/jnn.2010.2636

22. Liu X, Li R, Yuan X, et al., 2021, Fast Customization of Microneedle Arrays by Static Optical Projection Lithography. ACS Appl Mater Interfaces, 13:60522–30. http://doi.org/10.1021/acsami.1c21489

23. Tan JY, Kim A, Kim JJ, 2021, Modeling, Characterization, and Fabrication of Bell-tip Microneedle Array by Diffraction and Self-aligned Lens Effects. Appl Phys Lett, 119:023501. http://doi.org/10.1063/5.0055073

24. Yang C, Yu Y, Wang X, et al., 2021, Cellular Fluidic-based Vascular Networks for Tissue Engineering. Eng Regen, 2:171–4. http://doi.org/10.1016/j.engreg.2021.09.006

25. Use of International Standard ISO-10993-1, 2020, Biological Evaluation of Medical Devices Part 1: Evaluation and Testing within a Risk Management Process. In: US Department of Health and Human Services FDA, Center for Devices and Radiological Health, Center for Biologics Evaluation and Research.

26. Lim SH, Tiew WJ, Zhang J, et al., 2020, Geometrical Optimisation of a Personalised Microneedle Eye Patch for Transdermal Delivery of Anti-wrinkle Small Peptide. Biofabrication, 12:035003. http://doi.org/10.1088/1758-5090/ab6d37

27. Zhang D, Das DB, Rielly CD, 2014, Microneedle Assisted Micro-Particle Delivery from Gene Guns: Experiments Using Skin-Mimicking Agarose Gel. J Pharm Sci, 103:613–27. http://doi.org/10.1002/jps.23835

28. Wang J, Yu J, Zhang Y, et al., 2019, Charge-switchable Polymeric Complex for Glucose-responsive Insulin Delivery in Mice and Pigs. Sci Adv, 5:eaaw4357. http://doi.org/10.1126/sciadv.aaw4357

29. Zhou C, Tang H, Zhang L, et al., 2021, Hollow Microneedle Arrays Produced by Low‐Cost, High‐Fidelity Replication of Hypodermic Needle Tips for High‐Dose Transdermal Drug Delivery. Adv Eng Mater, 23:2001355. http://doi.org/10.1002/adem.202001355

30. Oskui SM, Diamante G, Liao C, et al., 2016, Assessing and Reducing the Toxicity of 3D-Printed Parts. Environ Sci Technol Lett, 3:1–6. http://doi.org/10.1021/acs.estlett.5b00249

31. Davis SP, Landis BJ, Adams ZH, et al., 2004, Insertion of Microneedles into Skin: Measurement and Prediction of Insertion Force and Needle Fracture Force. J Biomech, 37:1155–63. http://doi.org/10.1016/j.jbiomech.2003.12.010

32. Roxhed N, Samel B, Nordquist L, et al., 2008, Painless Drug Delivery through Microneedle-based Transdermal Patches Featuring Active Infusion. IEEE Trans Biomed Eng, 55:1063–71. http://doi.org/10.1109/TBME.2007.906492

33. Burton SA, Ng CY, Simmers R, et al., 2011, Rapid Intradermal Delivery of Liquid Formulations Using a Hollow Microstructured Array. Pharm Res, 28:31–40. http://doi.org/10.1007/s11095-010-0177-8

34. Ma Y, Li CG, Kim S, et al., 2018, An Insulin Microneedle Pen (IMP) for Self-Subcutaneous Insulin Injection. Adv Mater Technol, 3:1800234. http://doi.org/10.1002/admt.201800234

35. Jung YS, Koo DH, Yang JY, et al., 2018, Peri-tumor Administration of 5-fluorouracil Sol-gel Using a Hollow Microneedle for Treatment of Gastric Cancer. Drug Deliv, 25:872–9. http://doi.org/10.1080/10717544.2018.1455760

36. Dul M, Stefanidou M, Porta P, et al., 2017, Hydrodynamic Gene Delivery in Human Skin Using a Hollow Microneedle Device. J Control Release, 265:120–31. http://doi.org/10.1016/j.jconrel.2017.02.028

37. Norman JJ, Brown MR, Raviele NA, et al., 2013, Faster Pharmacokinetics and Increased Patient Acceptance of Intradermal Insulin Delivery Using a Single Hollow Microneedle in Children and Adolescents with Type 1 Diabetes. Pediatr Diabetes, 14:459–65. http://doi.org/10.1111/pedi.12031

38. Ogai N, Nonaka I, Toda Y, et al., 2018, Enhanced Immunity in Intradermal Vaccination by Novel Hollow Microneedles. Skin Res Technol, 24:630–5. http://doi.org/10.1111/srt.12576

39. Chen G, Chen Z, Wen D, et al., 2020, Transdermal Cold Atmospheric Plasma-mediated Immune Checkpoint Blockade Therapy. Proc Natl Acad Sci U S A, 117:3687–92. http://doi.org/10.1073/pnas.1917891117

40. Jun H, Han MR, Kang NG, et al., 2015, Use of Hollow Microneedles for Targeted Delivery of Phenylephrine to Treat Fecal Incontinence. J Control Release, 207:1–6. http://doi.org/10.1016/j.jconrel.2015.03.031

41. Szeto B, Aksit A, Valentini C, et al., 2020, Novel 3D-printed Hollow Microneedles Facilitate Safe, Reliable, and Informative Sampling of Perilymph from Guinea Pigs. Hear Res, 400:108141. http://doi.org/10.1016/j.heares.2020.108141

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