Microneedling Drug Delivery System: Strategies, Design, Manufacturing, Clinical Aspects and Treatment for Cancer Therapy
Abstract
Microneedling, a minimally invasive technique traditionally used in dermatology, has emerged as a promising approach to cancer therapy. The procedure involves creating microchannels in the skin using fine needles, enhancing the delivery of therapeutic agents directly into tumor tissues. This method overcomes the limitations of conventional cancer treatments, such as systemic toxicity and poor drug penetration, by facilitating localized and controlled drug delivery. Microneedling can also stimulate immune responses and induce tissue regeneration, potentially enhancing the effectiveness of immunotherapy and promoting tumor suppression. Recent studies have shown that microneedling can be combined with nanoparticles, chemotherapeutics, or gene therapies, allowing for a more precise and targeted treatment of cancer cells while minimizing damage to healthy tissues. Additionally, microneedling-based drug delivery systems can improve the bioavailability of drugs, reducing required dosages and associated side effects. The technique has been instrumental in treating skin cancers, such as melanoma, but its potential application in other solid tumors is currently being explored. While promising, further clinical studies are needed to optimize microneedling parameters and evaluate its long-term safety and efficacy in cancer therapy. As the field progresses, microneedling may revolutionize the delivery of cancer therapeutics, offering a cost-effective, patient-friendly option that complements existing treatments.
Keywords: Microneedling, Cancer therapy, Nanoparticles, Immunotherapy.
Keywords:
Microneedling, Cancer therapy, Nanoparticles, ImmunotherapyDOI
https://doi.org/10.22270/jddt.v14i12.6881References
1. Vander Heiden MG, DeBerardinis RJ. Understanding the Intersections between Metabolism and Cancer Biology. Cell. 2017;168(4):657-69. https://doi.org/10.1016/j.cell.2016.12.039 PMid:28187287 PMCid:PMC5329766
2. Lambert AW, Pattabiraman DR, Weinberg RA. Emerging biological principles of metastasis. Cell. 2017;168(4):670-91. https://doi.org/10.1016/j.cell.2016.11.037 PMid:28187288 PMCid:PMC5308465
3. Schiller JT, Lowy DR. An introduction to virus infections and human cancer. Viruses Hum cancer from basic Sci to Clin Prev. 2021;1-11. https://doi.org/10.1007/978-3-030-57362-1_1 PMid:33200359 PMCid:PMC8336782
4. Johnson DB, Singh G, Sharma D, Natarajan V, Lakshmi KC, Dhakar RC, Tiwari R, Exploring Computational Advancements in ADME: Essential Insights for Drug Disposition, Chinese journal of applied physiology, 2024;40:e20240032 https://doi.org/10.62958/j.cjap.2024.032 PMID: 39467652
5. Ganeson K, Alias AH, Murugaiyah V, Amirul AAA, Ramakrishna S, Vigneswari S. Microneedles for efficient and precise drug delivery in cancer therapy. Pharmaceutics. 2023;15(3):744. https://doi.org/10.3390/pharmaceutics15030744 PMid:36986606 PMCid:PMC10057903
6. Yang J, Liu X, Fu Y, Song Y. Recent advances of microneedles for biomedical applications: drug delivery and beyond. Acta Pharm Sin B. 2019;9(3):469-83. https://doi.org/10.1016/j.apsb.2019.03.007 PMid:31193810 PMCid:PMC6543086
7. Singh V, Kesharwani P. Recent advances in microneedles-based drug delivery device in the diagnosis and treatment of cancer. J Control Release. 2021;338:394-409. https://doi.org/10.1016/j.jconrel.2021.08.054 PMid:34481019
8. Seetharam AA, Choudhry H, Bakhrebah MA, Abdulaal WH, Gupta MS, Rizvi SMD, et al. Microneedles drug delivery systems for treatment of cancer: A recent update. Pharmaceutics. 2020;12(11):1101. https://doi.org/10.3390/pharmaceutics12111101 PMid:33212921 PMCid:PMC7698361
9. Chen S, Miyazaki T, Itoh M, Matsumoto H, Moro-oka Y, Tanaka M, et al. Temperature-stable boronate gel-based microneedle technology for self-regulated insulin delivery. ACS Appl Polym Mater. 2020;2(7):2781-90. https://doi.org/10.1021/acsapm.0c00341
10. Lahiji SF, Jang Y, Ma Y, Dangol M, Yang H, Jang M, et al. Effects of dissolving microneedle fabrication parameters on the activity of encapsulated lysozyme. Eur J Pharm Sci. 2018;117:290-6. https://doi.org/10.1016/j.ejps.2018.03.003 PMid:29505815
11. Dharadhar S, Majumdar A, Dhoble S, Patravale V. Microneedles for transdermal drug delivery: a systematic review. Drug Dev Ind Pharm. 2019;45(2):188-201. https://doi.org/10.1080/03639045.2018.1539497 PMid:30348022
12. Ye Y, Yu J, Wen D, Kahkoska AR, Gu Z. Polymeric microneedles for transdermal protein delivery. Adv Drug Deliv Rev. 2018;127:106-18. https://doi.org/10.1016/j.addr.2018.01.015 PMid:29408182 PMCid:PMC6020694
13. Nam K, Lee K, Youngwook CHO, Oh D. Composition for improving skin conditions comprising a fragment of human heat shock protein 90A as an active ingredient. Google Patents; 2020.
14. Zsikó S, Csányi E, Kovács A, Budai-Szűcs M, Gácsi A, Berkó S. Methods to evaluate skin penetration in vitro. Sci Pharm. 2019;87(3):19. https://doi.org/10.3390/scipharm87030019
15. Wang M, Hu L, Xu C. Recent advances in the design of polymeric microneedles for transdermal drug delivery and biosensing. Lab Chip. 2017;17(8):1373-87. https://doi.org/10.1039/C7LC00016B PMid:28352876
16. Ramaut L, Hoeksema H, Pirayesh A, Stillaert F, Monstrey S. Microneedling: Where do we stand now? A systematic review of the literature. J Plast Reconstr Aesthetic Surg. 2018;71(1):1-14. https://doi.org/10.1016/j.bjps.2017.06.006 PMid:28690124
17. Cheng X, Hu S, Cheng K. Microneedle patch delivery of PROTACs for anti-cancer therapy. ACS Nano. 2023;17(12):11855-68. https://doi.org/10.1021/acsnano.3c03166 PMid:37294705 PMCid:PMC11393661
18. Gadag S, Narayan R, Nayak AS, Ardila DC, Sant S, Nayak Y, et al. Development and preclinical evaluation of microneedle-assisted resveratrol loaded nanostructured lipid carriers for localized delivery to breast cancer therapy. Int J Pharm. 2021;606:120877. https://doi.org/10.1016/j.ijpharm.2021.120877 PMid:34252522 PMCid:PMC8429179
19. Mbituyimana B, Ma G, Shi Z, Yang G. Polymeric microneedles for enhanced drug delivery in cancer therapy. Biomater Adv. 2022;142:213151. https://doi.org/10.1016/j.bioadv.2022.213151 PMid:36244246
20. Zandi A, Khayamian MA, Saghafi M, Shalileh S, Katebi P, Assadi S, et al. Microneedle‐based generation of microbubbles in cancer tumors to improve ultrasound‐assisted drug delivery. Adv Healthc Mater. 2019;8(17):1900613. https://doi.org/10.1002/adhm.201900613 PMid:31328442
21. Uddin MJ, Scoutaris N, Economidou SN, Giraud C, Chowdhry BZ, Donnelly RF, et al. 3D printed microneedles for anticancer therapy of skin tumours. Mater Sci Eng C. 2020;107:110248. https://doi.org/10.1016/j.msec.2019.110248 PMid:31761175
22. Gualeni B, Coulman SA, Shah D, Eng PF, Ashraf H, Vescovo P, et al. Minimally invasive and targeted therapeutic cell delivery to the skin using microneedle devices. Br J Dermatol. 2018;178(3):731-9. https://doi.org/10.1111/bjd.15923 PMid:28865105
23. Borgheti-Cardoso LN, Viegas JSR, Silvestrini AVP, Caron AL, Praca FG, Kravicz M, et al. Nanotechnology approaches in the current therapy of skin cancer. Adv Drug Deliv Rev. 2020;153:109-36. https://doi.org/10.1016/j.addr.2020.02.005 PMid:32113956
24. Li X, Zhao Z, Zhang M, Ling G, Zhang P. Research progress of microneedles in the treatment of melanoma. J Control release. 2022;348:631-47. https://doi.org/10.1016/j.jconrel.2022.06.021 PMid:35718209
25. Xu N, Xu W, Zhang M, Yu J, Ling G, Zhang P. Microneedle‐Based Technology: Toward Minimally Invasive Disease Diagnostics. Adv Mater Technol. 2022;7(9):2101595. https://doi.org/10.1002/admt.202101595
26. Dardano P, Rea I, De Stefano L. Microneedles-based electrochemical sensors: New tools for advanced biosensing. Curr Opin Electrochem. 2019;17:121-7. https://doi.org/10.1016/j.coelec.2019.05.012
27. Shikida M, Hasegawa Y, Al Farisi MS, Matsushima M, Kawabe T. Advancements in MEMS technology for medical applications: Microneedles and miniaturized sensors. Jpn J Appl Phys. 2021;61(SA):SA0803. https://doi.org/10.35848/1347-4065/ac305d
28. Chang H, Zheng M, Yu X, Than A, Seeni RZ, Kang R, et al. A Swellable Microneedle Patch to Rapidly Extract Skin Interstitial Fluid for Timely Metabolic Analysis. Adv Mater. 2017 Oct;29(37):1702243. https://doi.org/10.1002/adma.201702243 PMid:28714117
29. Li CG, Joung HA, Noh H, Song MB, Kim MG, Jung H. One-touch-activated blood multidiagnostic system using a minimally invasive hollow microneedle integrated with a paper-based sensor. Lab Chip. 2015;15(16):3286-92. https://doi.org/10.1039/C5LC00669D PMid:26190447
30. Jin Q, Chen HJ, Li X, Huang X, Wu Q, He G, et al. Reduced Graphene Oxide Nanohybrid-Assembled Microneedles as Mini-Invasive Electrodes for Real-Time Transdermal Biosensing. Small. 2019 Feb;15(6):1804298. https://doi.org/10.1002/smll.201804298 PMid:30605244
31. Keum DH, Jung HS, Wang T, Shin MH, Kim YE, Kim KH, et al. Microneedle Biosensor for Real-Time Electrical Detection of Nitric Oxide for In Situ Cancer Diagnosis During Endomicroscopy. Adv Healthc Mater. 2015 Jun;4(8):1153-8. https://doi.org/10.1002/adhm.201500012 PMid:25728402
32. Tang L, Li Y, Xie H, Shu Q, Yang F, Liu Y ling, et al. A sensitive acupuncture needle microsensor for real-time monitoring of nitric oxide in acupoints of rats. Sci Rep. 2017;7(1):6446. https://doi.org/10.1038/s41598-017-06657-3 PMid:28744003 PMCid:PMC5527006
33. Mandal A, Boopathy A V, Lam LKW, Moynihan KD, Welch ME, Bennett NR, et al. Cell and fluid sampling microneedle patches for monitoring skin-resident immunity. Sci Transl Med. 2018 Nov;10(467):eaar2227. https://doi.org/10.1126/scitranslmed.aar2227 PMid:30429353
34. Miller PR, Xiao X, Brener I, Burckel DB, Narayan R, Polsky R. Diagnostic Devices: Microneedle-Based Transdermal Sensor for On-Chip Potentiometric Determination of K+ (Adv. Healthcare Mater. 6/2014). Adv Healthc Mater. 2014 Jun;3(6):948. https://doi.org/10.1002/adhm.201470032
35. Parrilla M, Cuartero M, Padrell Sánchez S, Rajabi M, Roxhed N, Niklaus F, et al. Wearable All-Solid-State Potentiometric Microneedle Patch for Intradermal Potassium Detection. Anal Chem. 2019 Jan;91(2):1578-86. https://doi.org/10.1021/acs.analchem.8b04877 PMid:30543102
36. Huang H, Qu M, Zhou Y, Cao W, Huang X, Sun J, et al. A microneedle patch for breast cancer screening via minimally invasive interstitial fluid sampling. Chem Eng J. 2023;472:145036. https://doi.org/10.1016/j.cej.2023.145036
37. Heikal LA, Ashour AA, Aboushanab AR, El-Kamel AH, Zaki II, El-Moslemany RM. Microneedles integrated with atorvastatin-loaded pumpkisomes for breast cancer therapy: A localized delivery approach. J Control Release. 2024;376:354-68. https://doi.org/10.1016/j.jconrel.2024.10.013 PMid:39413849
38. Mojeiko G, de Brito M, Salata GC, Lopes LB. Combination of microneedles and microemulsions to increase celecoxib topical delivery for potential application in chemoprevention of breast cancer. Int J Pharm. 2019;560:365-76. https://doi.org/10.1016/j.ijpharm.2019.02.011 PMid:30772460
39. Fan M, Zheng J, Huang Y, Lu H, Lu M. Transdermal therapeutic systems in breast cancer therapy. J Drug Deliv Sci Technol. 2023;105139. https://doi.org/10.1016/j.jddst.2023.105139
40. Li Y, Liang C, Zhou X. The application prospects of honokiol in dermatology. Dermatol Ther. 2022;35(8):e15658. https://doi.org/10.1111/dth.15658
41. Hegde AR, Raychaudhuri R, Pandey A, Kalthur G, Mutalik S. Exploring potential formulation strategies for chemoprevention of breast cancer: a localized delivery perspective. Nanomedicine. 2021;16(13):1111-32. https://doi.org/10.2217/nnm-2021-0018 PMid:33949895
42. Patil A, Narvenker R, Prabhakar B, Shende P. Strategic consideration for effective chemotherapeutic transportation via transpapillary route in breast cancer. Int J Pharm. 2020;586:119563. https://doi.org/10.1016/j.ijpharm.2020.119563 PMid:32569813
43. Chen L, Zhang C, Xiao J, You J, Zhang W, Liu Y, et al. Local extraction and detection of early stage breast cancers through a microneedle and nano-Ag/MBL film based painless and blood-free strategy. Mater Sci Eng C. 2020;109:110402. https://doi.org/10.1016/j.msec.2019.110402 PMid:32228911
44. Ma J, Tai Z, Li Y, Li Y, Wang J, Zhou T, et al. Dissolving Microneedle-Based Cascade-Activation Nanoplatform for Enhanced Photodynamic Therapy of Skin Cancer. Int J Nanomedicine. 2024;2057-70. https://doi.org/10.2147/IJN.S443835 PMid:38482522 PMCid:PMC10932757
45. Shao J, Li X, Li Y, Lin J, Huang P. Self‐Heating Multistage Microneedle Patch for Topical Therapy of Skin Cancer. Adv Mater. 2024;36(15):2308217. https://doi.org/10.1002/adma.202308217 PMid:38198412
46. Gu Z, Wang C, Ye Y. Enhanced cancer immunotherapy by microneedle patch-assisted delivery. Google Patents; 2024.
47. Edelson J. Transdermal delivery of large agents. Google Patents; 2018.
48. Edelson J. Improved delivery of large agents. Google Patents; 2020.
49. Lu Y, Mantha SN, Crowder DC, Chinchilla S, Shah KN, Yun YH, et al. Microstereolithography and characterization of poly(propylene fumarate)-based drug-loaded microneedle arrays. Biofabrication. 2015;7(4):45001. https://doi.org/10.1088/1758-5090/7/4/045001 PMid:26418306
50. Hamdan IMN, Tekko IA, Matchett KB, Arnaut LG, Silva CS, McCarthy HO, et al. Intradermal delivery of a near-infrared photosensitizer using dissolving microneedle arrays. J Pharm Sci. 2018;107(9):2439-50. https://doi.org/10.1016/j.xphs.2018.05.017 PMid:29864428
51. Al-Mayahy MH, Sabri AH, Rutland CS, Holmes A, McKenna J, Marlow M, et al. Insight into imiquimod skin permeation and increased delivery using microneedle pre-treatment. Eur J Pharm Biopharm. 2019;139:33-43. https://doi.org/10.1016/j.ejpb.2019.02.006 PMid:30771455
52. Sabri A, Ogilvie J, McKenna J, Segal J, Scurr D, Marlow M. Intradermal delivery of an immunomodulator for basal cell carcinoma; expanding the mechanistic insight into solid microneedle-enhanced delivery of hydrophobic molecules. Mol Pharm. 2020;17(8):2925-37. PMid:32510228 https://doi.org/10.1021/acs.molpharmaceut.0c00347
53. Ye C, Zhang R. Semiconductor Microneedle Assembly Based on Gene Therapy, Manufacturing Method and Manufacturing Mold. Chinese Pat CN106426729A. 2016;9.
54. Alshammari MK, Albutayh BNA, Alhabib B, Alharbi AS, Almutairi YS, Kamal M, et al. Cancer theranostics employing microneedles: Experimental and patented strategies. J Drug Deliv Sci Technol. 2023;83:104402. https://doi.org/10.1016/j.jddst.2023.104402
55. Wani A, Kasture K, Nigade O, Nadar D, Shende P. Potential of different types of microneedles in diagnosis and treatment of cancer. In: Design and Applications of Microneedles in Drug Delivery and Therapeutics. Elsevier; 2024. p. 343-77. https://doi.org/10.1016/B978-0-443-13881-2.00017-5
56. Chen MY, Chen YY, Tsai HT, Tzai TS, Chen MC, Tsai YS. Transdermal delivery of luteinizing hormone-releasing hormone with chitosan microneedles: a promising tool for androgen deprivation therapy. Anticancer Res. 2017;37(12):6791-7. https://doi.org/10.21873/anticanres.12139
57. Choi S, Kim Y, Lee JW, Park J, Prausnitz MR, Allen MG. Intracellular protein delivery and gene transfection by electroporation using a microneedle electrode array. Small. 2012;8(7):1081-91. https://doi.org/10.1002/smll.201101747 PMid:22328093 PMCid:PMC3516926
58. Choi SO, Kim YC, Park JH, Hutcheson J, Gill HS, Yoon YK, et al. An electrically active microneedle array for electroporation. Biomed Microdevices. 2010;12:263-73. https://doi.org/10.1007/s10544-009-9381-x PMid:20012696 PMCid:PMC2905216
59. Cole G, Ali AA, McErlean E, Mulholland EJ, Short A, McCrudden CM, et al. DNA vaccination via RALA nanoparticles in a microneedle delivery system induces a potent immune response against the endogenous prostate cancer stem cell antigen. Acta Biomater. 2019;96:480-90. https://doi.org/10.1016/j.actbio.2019.07.003 PMid:31299353
Published
Abstract Display: 673 
PDF Downloads: 466 PDF Downloads: 124 How to Cite
Issue
Section
Copyright (c) 2024 Priyanshu Sharma, Abhishek Singh, Kapil Kumar Verma , Inder Kumar
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors who publish with this journal agree to the following terms:
- Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0). that allows others to share the work with an acknowledgment of the work's authorship and initial publication in this journal.
- Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgment of its initial publication in this journal.
- Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).
How to Cite
.