Biosensors and Nanotheranostics
Bionanotechnology, Drug Delivery, Therapeutics | online ISSN 3064-7789
113
Citations
99.4k
Views
64
Articles
Volume 4 Number 1 2025
REVIEWS (Open Access)
Nanomaterial-Enhanced Microneedles for Interstitial Fluid Glucose Sensing and Transdermal Drug Delivery: A Review
Kamilia Badrina Mohamed Kamal 1, Anisah Najwa 1, HA Latib 1, Fouad Saleh AL Suede 1*
Biosensors and Nanotheranostics 4 (1) 1-11 https://doi.org/10.25163/biosciences.4110523
Submitted: 27 July 2025 Revised: 18 September 2025 Accepted: 24 September 2025 Published: 25 September 2025
Abstract
Microneedle (MN) platforms have moved from laboratory curiosities toward genuinely usable tools for minimally invasive interstitial fluid (ISF) sampling and transdermal therapy, and nanomaterial integration is often credited with much of that progress — though how consistently, and how well-supported by data, has not been carefully mapped. Following PRISMA 2020 guidance, we searched PubMed, Scopus, Web of Science, and Google Scholar for studies published up to 2025 describing nanomaterial-enhanced microneedle (NE-MN) systems used for ISF biosensing or therapeutic delivery. Nineteen studies met eligibility criteria after title/abstract and full-text screening. Because reported outcomes varied too widely in metric, model, and analyte to be statistically pooled, findings were synthesized narratively rather than meta-analytically. Diagnostic NE-MN studies reported R² values between 0.85 and 0.981 for glucose sensing in animal or in vitro models, alongside a limit of detection of 3.7 μM for an aptamer-based drug-monitoring sensor; no included NE-MN study reported a correlation coefficient or MARD directly comparable across platforms. Therapeutic NE-MN systems showed more quantifiable, comparable outcomes, including 91.5% apoptosis with 41.78% permeation efficiency in a PEGylated-liposome hydrogel patch, alongside reproducible reductions in adiposity and infection burden in animal models. A non-nanomaterial CGM validation study is discussed separately to illustrate physiological ISF-blood lag under exercise, not as NE-MN evidence. Nanomaterial integration shows credible, if still sparsely quantified, gains in sensing performance and clear therapeutic promise in preclinical models; the field currently lacks the standardized, comparable accuracy reporting needed for formal meta-analysis, which we identify as the most pressing methodological gap.
Keywords: Microneedles; Nanomaterials; Interstitial Fluid; Glucose Biosensing; Transdermal Drug Delivery
References
Abbasi, M., Boka, D. A., & DeLoit, H. (2024). Nanomaterial-enhanced microneedles: Emerging therapies for diabetes and obesity. Pharmaceutics, 16(10), 1344. https://doi.org/10.3390/pharmaceutics16101344
Ahmed, Y. M., Eldin, M. A., Galal, A., & Atta, N. F. (2024). Electrochemical sensor based on PEDOT/CNTs-graphene oxide for simultaneous determination of hazardous hydroquinone, catechol, and nitrite in real water samples. Scientific Reports, 14(1), 5654. https://doi.org/10.1038/s41598-024-54683-9
Aldawood, F. K., Andar, A., & Desai, S. (2021). A comprehensive review of microneedles: Types, materials, processes, characterizations and applications. Polymers, 13(16), 2815. https://doi.org/10.3390/polym13162815
Alimardani, V., Abolmaali, S. S., Yousefi, G., Rahiminezhad, Z., Abedi, M., Tamaddon, A., & Ahadian, S. (2021). Microneedle arrays combined with nanomedicine approaches for transdermal delivery of therapeutics. Journal of Clinical Medicine, 10(1), 181. https://doi.org/10.3390/jcm10020181
Ashraf, G., Ahmed, K., Aziz, A., Asif, M., Kong, J., & Fang, X. (2025). Microneedle wearables in advanced microsystems: Unlocking next-generation biosensing with AI. TrAC Trends in Analytical Chemistry, 187, 118208. https://doi.org/10.1016/j.trac.2025.118208
Bauhaus, H., Erdogan, P., Braun, H., & Thevis, M. (2023). Continuous glucose monitoring (CGM) in sports—A comparison between a CGM device and lab-based glucose analyser under resting and exercising conditions in athletes. International Journal of Environmental Research and Public Health, 20(15), 6440. https://doi.org/10.3390/ijerph20156440
Bollella, P., Sharma, S., Cass, A. E. G., & Antiochia, R. (2019). Minimally-invasive microneedle-based biosensor array for simultaneous lactate and glucose monitoring in artificial interstitial fluid. Electroanalysis, 31(2), 374–382. https://doi.org/10.1002/elan.201800630
Borenstein, M., Hedges, L. V., Higgins, J. P. T., & Rothstein, H. R. (2009). Introduction to meta-analysis. Wiley. https://doi.org/10.1002/9780470743386
Bowler, A.-L. M., Whitfield, J., Marshall, L., Coffey, V. G., Burke, L. M., & Cox, G. R. (2023). The use of continuous glucose monitors in sport: Possible applications and considerations. International Journal of Sport Nutrition and Exercise Metabolism, 33, 121–132. https://doi.org/10.1123/ijsnem.2022-0139
Caffarel-Salvador, E., Brady, A. J., Eltayib, E., Meng, T., Alonso-Vicente, A., Gonzalez-Vazquez, P., Torrisi, B. M., Vicente-Perez, E. M., Mooney, K., Jones, D. S., Coulter, J. A., McCarthy, H. O., McElnay, J. C., & Donnelly, R. F. (2015). Hydrogel-forming microneedle arrays allow detection of drugs and glucose in vivo: Potential for use in diagnosis and therapeutic drug monitoring. PLoS ONE, 10(12), e0145644. https://doi.org/10.1371/journal.pone.0145644
Cai, G., Li, R., Chai, X., Cai, X., Zheng, K., Wang, Y., Fan, K., Guo, Z., Guo, J., & Jiang, W. (2024). Catalase-templated nanozyme-loaded microneedles integrated with polymyxin B for immunoregulation and antibacterial activity in diabetic wounds. Journal of Colloid and Interface Science, 667, 529–542. https://doi.org/10.1016/j.jcis.2024.04.121
Cha, S., Choi, M. Y., Kim, M. J., Sim, S. B., Haizan, I., & Choi, J.-H. (2025). Electrochemical microneedles for real-time monitoring in interstitial fluid: Emerging technologies and future directions. Biosensors, 15(6), 380. https://doi.org/10.3390/bios15060380
Chen, H., Zhu, H., Zheng, J., Mou, D., Wan, J., Zhang, J., Shi, T., Zhao, Y., Xu, H., & Yang, X. (2009). Iontophoresis-driven penetration of nanovesicles through microneedle-induced skin microchannels for enhancing transdermal delivery of insulin. Journal of Controlled Release, 139(1), 63–72. https://doi.org/10.1016/j.jconrel.2009.05.031
Chen, Q., Xiao, Z., Wang, C., Chen, G., Zhang, Y., Zhang, X., Han, X., Wang, J., Ye, X., & Prausnitz, M. R. (2022). Microneedle patches loaded with nanovesicles for glucose transporter-mediated insulin delivery. ACS Nano, 16(11), 18223–18231. https://doi.org/10.1021/acsnano.2c05687
Chen, S., Wang, J., Sun, L., Xia, F., Li, W., Yuan, L., Liu, C., Li, P., Bao, C., & Wang, M. (2024). A quick plaster-type soluble nanoparticle microneedle patch for the treatment of obesity. Biomaterials, 311, 122687. https://doi.org/10.1016/j.biomaterials.2024.122687
Chien, M.-N., Chen, Y.-J., Bai, C.-H., & Huang, J.-T. (2022). Continuous glucose monitoring system based on percutaneous microneedle array. Micromachines, 13(3), 478. https://doi.org/10.3390/mi13030478
Choi, Y.-H., Piao, H., Lee, J., Kim, J., Choi, H.-J., & Khang, D.-Y. (2025). Flexible and stretchable microneedle electrode arrays by soft lithography for continuous monitoring of glucose. Biosensors, 15(9), 576. https://doi.org/10.3390/bios15090576
DerSimonian, R., & Laird, N. (1986). Meta-analysis in clinical trials. Controlled Clinical Trials, 7(3), 177–188. https://doi.org/10.1016/0197-2456(86)90046-2
Dervisevic, M., Harberts, J., Sánchez-Salcedo, R., & Voelcker, N. H. (2024). 3D polymeric lattice microstructure-based microneedle array for transdermal electrochemical biosensing. Advanced Materials, 36, 2412999. https://doi.org/10.1002/adma.202412999
Dong, L., Ren, S., Zhang, X., Yang, Y., Wu, Q., & Lei, T. (2023). In-situ synthesis of Pt nanoparticles/reduced graphene oxide/cellulose nanohybrid for nonenzymatic glucose sensing. Carbohydrate Polymers, 303, 120463. https://doi.org/10.1016/j.carbpol.2022.120463
Downs, A. M., Bolotsky, A., Weaver, B. M., Bennett, H., Wolff, N., Polsky, R., & Miller, P. R. (2023). Microneedle electrochemical aptamer-based sensing: Real-time small molecule measurements using sensor-embedded, commercially available stainless-steel microneedles. Biosensors and Bioelectronics, 236, 115408. https://doi.org/10.1016/j.bios.2023.115408
Freckmann, G., Pleus, S., Grady, M., Setford, S., & Levy, B. (2019). Measures of accuracy for continuous glucose monitoring and blood glucose monitoring devices. Journal of Diabetes Science and Technology, 13(3), 575–583. https://doi.org/10.1177/1932296818812062
GhavamiNejad, P., GhavamiNejad, A., Zheng, H., Dhingra, K., Samarikhalaj, M., & Poudineh, M. (2023). A conductive hydrogel microneedle-based assay integrating PEDOT:PSS and Ag–Pt nanoparticles for real-time, enzyme-less, and electrochemical sensing of glucose. Advanced Healthcare Materials, 12(15), 2202362. https://doi.org/10.1002/adhm.202202362
Higgins, J. P. T., Thomas, J., Chandler, J., Cumpston, M., Li, T., Page, M. J., & Welch, V. A. (2022). Cochrane handbook for systematic reviews of interventions (Version 6.3). Cochrane. http://www.training.cochrane.org/handbook
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003). Measuring inconsistency in meta-analyses. BMJ, 327(7414), 557–560. https://doi.org/10.1136/bmj.327.7414.557
Huang, X., Liang, B., Zheng, S., Wu, F., He, M., Huang, S., Yang, J., Ouyang, Q., Liu, F., & Liu, J. (2024). Microarrow sensor array with enhanced skin adhesion for transdermal continuous monitoring of glucose and reactive oxygen species. Bio-Design and Manufacturing, 7(1), 14–30. https://doi.org/10.1007/s42242-023-00246-2
Page, M. J., McKenzie, J. E., Bossuyt, P. M., Boutron, I., Hoffmann, T. C., Mulrow, C. D., Shamseer, L., Tetzlaff, J. M., Akl, E. A., Brennan, S. E., Chou, R., Glanville, J., Grimshaw, J. M., Hróbjartsson, A., Lalu, M. M., Li, T., Loder, E. W., Mayo-Wilson, E., McDonald, S., … Moher, D. (2021). The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. BMJ, 372, n71. https://doi.org/10.1136/bmj.n71
Suriyaamporn, P., Pornpitchanarong, C., Charoenying, T., Dechsri, K., Ngawhirunpat, T., Opanasopit, P., & Pamornpathomkul, B. (2025). Artificial intelligence-driven hydrogel microneedle patches integrating 5-fluorouracil inclusion complex-loaded flexible pegylated liposomes for enhanced non-melanoma skin cancer treatment. International Journal of Pharmaceutics, 669, 125072. https://doi.org/10.1016/j.ijpharm.2024.125072
Teymourian, H., Moonla, C., Tehrani, F., Vargas, E., Aghavali, R., Barfidokht, A., Tangkuaram, T., Mercier, P. P., Dassau, E., & Wang, J. (2020). Microneedle-based detection of ketone bodies along with glucose and lactate: Toward real-time continuous interstitial fluid monitoring of diabetic ketosis and ketoacidosis. Analytical Chemistry, 92(4), 2291–2300. https://doi.org/10.1021/acs.analchem.9b05109
Zhu, J., Dangol, M., Yang, J., Xu, S., Kim, S., Kang, G., Jang, M., Kim, S., Yeom, H., & Jung, H. (2020). Gelatin methacryloyl microneedle patches for minimally invasive extraction of skin interstitial fluid. Small, 16(16), 1905905. https://doi.org/10.1002/smll.201905910
Recommended articles
From Waste to Water Cure: How Lignocellulosic Biomass-Derived Nanomaterials Are Redefining Sustainable Wastewater Remediation — A Systematic Review and Meta-Analysis
Quantum Dots in Biomedical and Environmental Applications: Insights from Systematic Review and Meta-Analysis
Engineering the Nanoscale: Transformative Roles of Nanomaterials in COVID-19 Diagnosis, Treatment, and Vaccine Development
1
Save
Save
0
Citation
Citation
521
View
View
0
Share
Share