Microneedles’ Device: Design, Fabrication, and Applications
Abstract
:1. Introduction
2. Types of Microneedles
2.1. Solid Microneedles
2.2. Coated Microneedles
2.3. Dissolving Microneedles
2.4. Hollow Microneedles
2.5. Hydrogel-Forming Microneedles
3. Microneedle Design
3.1. Length
3.2. Needle-to-Needle Spacing
3.3. Tip Diameter and Tip Angle
3.4. Aspect Ratio
3.5. Needle Geometry
4. Microneedle Fabrication Methods
4.1. Microelectromechanical Systems (MEMSs)
4.2. Micromolding
4.3. Laser Cutting
4.4. Laser Ablation
4.5. Drawing-Based Methods
4.6. Atomized Spraying Method
4.7. Injection Molding
4.8. Micro-Mechanical Machining
4.9. Additive Manufacturing
4.9.1. Fused Deposition Modelling (FDM)
4.9.2. Material Jetting (MJ)
4.9.3. Stereolithography (SLA)
4.9.4. Digital Light Processing (DLP)
4.9.5. Continuous Liquid Interface Production (CLIP)
4.9.6. Two-Photon Polymerization (2PP)
5. Microneedle System Applications
6. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Chuong, C.M.; Nickoloff, B.J.; Elias, P.M.; Goldsmith, L.A.; Macher, E.; Maderson, P.A.; Sundberg, J.P.; Tagami, H.; Plonka, P.M.; Thestrup-Pedersen, K.; et al. What is the “true” function of skin? Exp. Dermatol. 2002, 11, 159–160. [Google Scholar] [CrossRef]
- Chien, Y.W.; Liu, J.-C. Transdermal Drug Delivery Systems. J. Biomater. Appl. 1986, 1, 183–206. [Google Scholar] [CrossRef]
- Wong, W.F.; Ang, K.P.; Sethi, G.; Looi, C.Y. Recent Advancement of Medical Patch for Transdermal Drug Delivery. Medicina 2023, 59, 778. [Google Scholar] [CrossRef]
- Lasagna, L.; Greenblatt, D.J. More Than Skin Deep: Transdermal Drug-Delivery Systems. N. Engl. J. Med. 1986, 314, 1638–1639. [Google Scholar] [CrossRef]
- Zhou, Q.; Li, H.; Liao, Z.; Gao, B.; He, B. Bridging the Gap between Invasive and Noninvasive Medical Care: Emerging Microneedle Approaches. Anal. Chem. 2023, 95, 515–534. [Google Scholar] [CrossRef]
- Waghule, T.; Singhvi, G.; Dubey, S.K.; Pandey, M.M.; Gupta, G.; Singh, M.; Dua, K. Microneedles: A smart approach and increasing potential for transdermal drug delivery system. Biomed. Pharmacother. 2019, 109, 1249–1258. [Google Scholar] [CrossRef]
- Pettis, R.J.; Harvey, A.J.; Ham, A.S.; Buckheit, R.W.; Singla, S.K.; Sachdeva, V.; Shin, C.I.; Jeong, S.D.; Re**old, N.S.; Kim, Y.-C.; et al. Microneedle delivery: Clinical studies and emerging medical applications. Ther. Deliv. 2012, 3, 357–371. [Google Scholar] [CrossRef]
- Al-Japairai, K.A.S.; Mahmood, S.; Almurisi, S.H.; Venugopal, J.R.; Hilles, A.R.; Azmana, M.; Raman, S. Current trends in polymer microneedle for transdermal drug delivery. Int. J. Pharm. 2020, 587, 119673. [Google Scholar] [CrossRef]
- Yan, G.; Warner, K.S.; Zhang, J.; Sharma, S.; Gale, B.K. Evaluation needle length and density of microneedle arrays in the pretreatment of skin for transdermal drug delivery. Int. J. Pharm. 2010, 391, 7–12. [Google Scholar] [CrossRef] [PubMed]
- Xu, J.; Xu, D.; Xuan, X.; He, H. Advances of Microneedles in Biomedical Applications. Molecules 2021, 26, 5912. [Google Scholar] [CrossRef] [PubMed]
- Sachan, A.; Sachan, R.J.; Lu, J.; Sun, H.; **, Y.J.; Erdmann, D.; Zhang, J.Y.; Narayan, R.J. Injection molding for manufacturing of solid poly(l-lactide-co-glycolide) microneedles. MRS Adv. 2021, 6, 61–65. [Google Scholar] [CrossRef]
- **, X.; Zhu, D.D.; Chen, B.Z.; Ashfaq, M.; Guo, X.D. Insulin delivery systems combined with microneedle technology. Adv. Drug Deliv. Rev. 2018, 127, 119–137. [Google Scholar] [CrossRef] [PubMed]
- Luo, X.; Yu, Q.; Liu, Y.; Gai, W.; Ye, L.; Yang, L.; Cui, Y. Closed-Loop Diabetes Minipatch Based on a Biosensor and an Electroosmotic Pump on Hollow Biodegradable Microneedles. ACS Sens. 2022, 7, 1347–1360. [Google Scholar] [CrossRef] [PubMed]
- Han, D.; Morde, R.S.; Mariani, S.; La Mattina, A.A.; Vignali, E.; Yang, C.; Barillaro, G.; Lee, H. 4D Printing of a Bioinspired Microneedle Array with Backward-Facing Barbs for Enhanced Tissue Adhesion. Adv. Funct. Mater. 2020, 30, 1909197. [Google Scholar] [CrossRef]
- Kim, Y.-C.; Park, J.-H.; Prausnitz, M.R. Microneedles for drug and vaccine delivery. Adv. Drug Deliv. Rev. 2012, 64, 1547–1568. [Google Scholar] [CrossRef] [PubMed]
- Lee, G.; Ma, Y.; Lee, Y.-H.; Jung, H. Clinical Evaluation of a Low-pain Long Microneedle for Subcutaneous Insulin Injection. BioChip J. 2018, 12, 309–316. [Google Scholar] [CrossRef]
- Zhang, R.; Miao, Q.; Deng, D.; Wu, J.; Miao, Y.; Li, Y. Research progress of advanced microneedle drug delivery system and its application in biomedicine. Colloids Surf. B Biointerfaces 2023, 226, 113302. [Google Scholar] [CrossRef]
- Parhi, R. Recent advances in 3D printed microneedles and their skin delivery application in the treatment of various diseases. J. Drug Deliv. Sci. Technol. 2023, 84, 104395. [Google Scholar] [CrossRef]
- Yang, G.; Chen, Q.; Wen, D.; Chen, Z.; Wang, J.; Chen, G.; Wang, Z.; Zhang, X.; Zhang, Y.; Hu, Q.; et al. A Therapeutic Microneedle Patch Made from Hair-Derived Keratin for Promoting Hair Regrowth. ACS Nano 2019, 13, 4354–4360. [Google Scholar] [CrossRef] [PubMed]
- Barnum, L.; Samandari, M.; Schmidt, T.A.; Tamayol, A. Microneedle arrays for the treatment of chronic wounds. Expert Opin. Drug Deliv. 2020, 17, 1767–1780. [Google Scholar] [CrossRef]
- Than, A.; Liu, C.; Chang, H.; Duong, P.K.; Cheung, C.M.G.; Xu, C.; Wang, X.; Chen, P. Self-implantable double-layered micro-drug-reservoirs for efficient and controlled ocular drug delivery. Nat. Commun. 2018, 9, 4433. [Google Scholar] [CrossRef] [PubMed]
- Ju, E.; Peng, M.; Xu, Y.; Wang, Y.; Zhou, F.; Wang, H.; Li, M.; Zheng, Y.; Tao, Y. Nanozyme-integrated microneedle patch for enhanced therapy of cutaneous squamous cell carcinoma by breaking the gap between H2O2 self-supplying chemodynamic therapy and photothermal therapy. J. Mater. Chem. B 2023, 11, 6595–6602. [Google Scholar] [CrossRef] [PubMed]
- Shukla, S.; Mamale, K.B.; Arya, R.K.; Kaundal, R.K.; Shukla, R. Therapeutic potential of microneedles based delivery systems for the management of atopic dermatitis. J. Drug Deliv. Sci. Technol. 2023, 84, 104493. [Google Scholar] [CrossRef]
- Cheng, X.; Hu, S.; Cheng, K. Microneedle Patch Delivery of PROTACs for Anti-Cancer Therapy. ACS Nano 2023, 17, 11855–11868. [Google Scholar] [CrossRef] [PubMed]
- Li, W.; Chen, J.Y.; Terry, R.N.; Tang, J.; Romanyuk, A.; Schwendeman, S.P.; Prausnitz, M.R. Core-shell microneedle patch for six-month controlled-release contraceptive delivery. J. Control. Release 2022, 347, 489–499. [Google Scholar] [CrossRef] [PubMed]
- Kim, Y.; Park, I.H.; Shin, J.; Choi, J.; Jeon, C.; Jeon, S.; Shin, J.; Jung, H. Sublingual Dissolving Microneedle (SLDMN)-based Vaccine for Inducing Mucosal Immunity Against SARS-CoV-2. Adv. Healthc. Mater. 2023, 12, 2300889. [Google Scholar] [CrossRef] [PubMed]
- Wang, L.; Yang, L.; Zhang, F.; Liu, X.; ** of biodegradable microneedle arrays by integrating CO2 laser processing and polymer molding. J. Micromech. Microeng. 2016, 26, 65015. [Google Scholar] [CrossRef]
- Demir, Y.K.; Akan, Z.; Kerimoglu, O. Characterization of Polymeric Microneedle Arrays for Transdermal Drug Delivery. PLoS ONE 2013, 8, e77289. [Google Scholar] [CrossRef]
- Anbazhagan, G.; Suseela, S.B.; Sankararajan, R. Design, analysis and fabrication of solid polymer microneedle patch using CO2 laser and polymer molding. Drug Deliv. Transl. Res. 2023, 13, 1813–1827. [Google Scholar] [CrossRef]
- Adarkwa, E.; Desai, S. Scalable Droplet Based Manufacturing Using In-Flight Laser Evaporation. J. Nanoeng. Nanomanuf. 2016, 6, 87–92. [Google Scholar] [CrossRef]
- Yang, M.; Xu, Z.; Desai, S.; Kumar, D.; Sankar, J. Fabrication of Micro Single Chamber Solid Oxide Fuel Cell Using Photolithography and Pulsed Laser Deposition. J. Fuel Cell Sci. Technol. 2015, 12, 021004. [Google Scholar] [CrossRef]
- Esho, T.; Desai, S. Laser based microdroplet evaporation towards scalable micro and nano manufacturing. In Proceedings of the 62nd IIE Annual Conference and Expo, Orlando, FL, USA, 19–23 May 2012; pp. 1750–1757. [Google Scholar]
- Parupelli, S.K.; Desai, S. Understanding Hybrid Additive Manufacturing of Functional Devices. Am. J. Eng. Appl. Sci. 2017, 10, 264–271. [Google Scholar] [CrossRef]
- McKenzie, J.; Desai, S. Investigating Sintering Mechanisms for Additive Manufacturing of Conductive Traces. Am. J. Eng. Appl. Sci. 2018, 11, 652–662. [Google Scholar] [CrossRef]
- Desai, S.; Craps, M.; Esho, T. Direct writing of nanomaterials for flexible thin-film transistors (fTFTs). Int. J. Adv. Manuf. Technol. 2013, 64, 537–543. [Google Scholar] [CrossRef]
- Ahmed, M.; El-Naggar, M.E.; Aldalbahi, A.; El-Newehy, M.H.; Menazea, A. Methylene blue degradation under visible light of metallic nanoparticles scattered into graphene oxide using laser ablation technique in aqueous solutions. J. Mol. Liq. 2020, 315, 113794. [Google Scholar] [CrossRef]
- Ismail, A.; El-Newehy, M.H.; El-Naggar, M.E.; Moydeen, A.M.; Menazea, A. Enhancement the electrical conductivity of the synthesized polyvinylidene fluoride/polyvinyl chloride composite doped with palladium nanoparticles via laser ablation. J. Mater. Res. Technol. 2020, 9, 11178–11188. [Google Scholar] [CrossRef]
- Menazea, A.; El-Newehy, M.H.; Thamer, B.M.; El-Naggar, M.E. Preparation of antibacterial film-based biopolymer embedded with vanadium oxide nanoparticles using one-pot laser ablation. J. Mol. Struct. 2021, 1225, 129163. [Google Scholar] [CrossRef]
- Tu, K.-T.; Chung, C.-K. Fabrication of biodegradable polymer microneedle array via CO2 laser ablation. In Proceedings of the 2015 IEEE 10th International Conference on Nano/Micro Engineered and Molecular Systems (NEMS), ** and customizable microneedle design: Ultra-sharp microneedle fabrication using two-photon polymerization and low-cost micromolding techniques. Manuf. Lett. 2021, 30, 39–43. [Google Scholar] [CrossRef]
- Pillai, M.M.; Ajesh, S.; Tayalia, P. Two-photon polymerization based reusable master template to fabricate polymer microneedles for drug delivery. MethodsX 2023, 10, 102025. [Google Scholar] [CrossRef] [PubMed]
- Fakeih, E.; Aguirre-Pablo, A.A.; Thoroddsen, S.T.; Salama, K.N. Fabrication and Characterization of Porous Microneedles for Enhanced Fluid Injection and Suction: A Two-Photon Polymerization Approach. Adv. Eng. Mater. 2023, 25, 2300161. [Google Scholar] [CrossRef]
- He, Z.; Chen, F.; He, S. Fabrication of microneedles using two photon-polymerization with low numerical aperture. Opt. Commun. 2024, 553, 130093. [Google Scholar] [CrossRef]
- Economidou, S.N.; Uddin, J.; Marques, M.J.; Douroumis, D.; Sow, W.T.; Li, H.; Reid, A.; Windmill, J.F.; Podoleanu, A. A novel 3D printed hollow microneedle microelectromechanical system for controlled, personalized transdermal drug delivery. Addit. Manuf. 2021, 38, 101815. [Google Scholar] [CrossRef]
- Rodgers, A.M.; McCrudden, M.T.C.; Vincente-Perez, E.M.; Dubois, A.V.; Ingram, R.J.; Larrañeta, E.; Kissenpfennig, A.; Donnelly, R.F. Design and characterisation of a dissolving microneedle patch for intradermal vaccination with heat-inactivated bacteria: A proof of concept study. Int. J. Pharm. 2018, 549, 87–95. [Google Scholar] [CrossRef]
- Boopathy, A.V.; Mandal, A.; Kulp, D.W.; Menis, S.; Bennett, N.R.; Watkins, H.C.; Wang, W.; Martin, J.T.; Thai, N.T.; He, Y.; et al. Enhancing humoral immunity via sustained-release implantable microneedle patch vaccination. Proc. Natl. Acad. Sci. USA 2019, 116, 16473–16478. [Google Scholar] [CrossRef] [PubMed]
- Park, J.; Kim, Y.-C. Topical delivery of 5-fluorouracil-loaded carboxymethyl chitosan nanoparticles using microneedles for keloid treatment. Drug Deliv. Transl. Res. 2020, 11, 205–213. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Sun, B.; Guo, J.; Wang, M.; Cui, H.; Mao, H.; Wang, B.; Yan, F. Active pharmaceutical ingredient poly(ionic liquid)-based microneedles for the treatment of skin acne infection. Acta Biomater. 2021, 115, 136–147. [Google Scholar] [CrossRef] [PubMed]
- Ning, X.; Wiraja, C.; Chew, W.T.S.; Fan, C.; Xu, C. Transdermal delivery of Chinese herbal medicine extract using dissolvable microneedles for hypertrophic scar treatment. Acta Pharm. Sin. B 2021, 11, 2937–2944. [Google Scholar] [CrossRef] [PubMed]
- Chen, Z.; Hu, X.; Lin, Z.; Mao, H.; Qiu, Z.; **ang, K.; Ke, T.; Li, L.; Lu, L.; **ao, L. Layered GelMA/PEGDA Hydrogel Microneedle Patch as an Intradermal Delivery System for Hypertrophic Scar Treatment. ACS Appl. Mater. Interfaces 2023, 15, 43309–43320. [Google Scholar] [CrossRef] [PubMed]
- Meng, S.; Wei, Q.; Chen, S.; Liu, X.; Cui, S.; Huang, Q.; Chu, Z.; Ma, K.; Zhang, W.; Hu, W.; et al. MiR-141-3p-Functionalized Exosomes Loaded in Dissolvable Microneedle Arrays for Hypertrophic Scar Treatment. Small 2023, 20, e2305374. [Google Scholar] [CrossRef]
- Huang, Y.; Li, J.; Wang, Y.; Chen, D.; Huang, J.; Dai, W.; Peng, P.; Guo, L.; Lei, Y. Intradermal delivery of an angiotensin II receptor blocker using a personalized microneedle patch for treatment of hypertrophic scars. Biomater. Sci. 2023, 11, 583–595. [Google Scholar] [CrossRef] [PubMed]
- Zhao, W.; Zheng, L.; Yang, J.; Li, Y.; Zhang, Y.; Ma, T.; Wang, Q. Dissolving microneedle patches-mediated percutaneous delivery of tetramethylpyrazine for rheumatoid arthritis treatment. Eur. J. Pharm. Sci. 2023, 184, 106409. [Google Scholar] [CrossRef]
- Ding, H.; Cui, Y.; Yang, J.; Li, Y.; Zhang, H.; Ju, S.; Ren, X.; Ding, C.; Zhao, J. ROS-responsive microneedles loaded with integrin avβ6-blocking antibodies for the treatment of pulmonary fibrosis. J. Control. Release 2023, 360, 365–375. [Google Scholar] [CrossRef]
- Ben David, N.; Richtman, Y.; Gross, A.; Ibrahim, R.; Nyska, A.; Ramot, Y.; Mizrahi, B. Design and Evaluation of Dissolvable Microneedles for Treating Atopic Dermatitis. Pharmaceutics 2023, 15, 1109. [Google Scholar] [CrossRef]
- Ye, G.; Jimo, R.; Lu, Y.; Kong, Z.; Axi, Y.; Huang, S.; **ong, Y.; Zhang, L.; Chen, G.; **ao, Y.; et al. Multifunctional natural microneedles based methacrylated Bletilla striata polysaccharide for repairing chronic wounds with bacterial infections. Int. J. Biol. Macromol. 2024, 254, 127914. [Google Scholar] [CrossRef] [PubMed]
- Long, L.-Y.; Liu, W.; Li, L.; Hu, C.; He, S.; Lu, L.; Wang, J.; Yang, L.; Wang, Y.-B. Dissolving microneedle-encapsulated drug-loaded nanoparticles and recombinant humanized collagen type III for the treatment of chronic wound via anti-inflammation and enhanced cell proliferation and angiogenesis. Nanoscale 2022, 14, 1285–1295. [Google Scholar] [CrossRef] [PubMed]
- Cai, Y.; Xu, X.; Wu, M.; Liu, J.; Feng, J.; Zhang, J. Multifunctional zwitterionic microneedle dressings for accelerated healing of chronic infected wounds in diabetic rat models. Biomater. Sci. 2023, 11, 2750–2758. [Google Scholar] [CrossRef] [PubMed]
- Lu, M.; Zhang, X.; Xu, D.; Li, N.; Zhao, Y. Encoded Structural Color Microneedle Patches for Multiple Screening of Wound Small Molecules. Adv. Mater. 2023, 35, e2211330. [Google Scholar] [CrossRef]
- Samant, P.P.; Niedzwiecki, M.M.; Raviele, N.; Tran, V.; Mena-Lapaix, J.; Walker, D.I.; Felner, E.I.; Jones, D.P.; Miller, G.W.; Prausnitz, M.R. Sampling interstitial fluid from human skin using a microneedle patch. Sci. Transl. Med. 2020, 12, eaaw0285. [Google Scholar] [CrossRef] [PubMed]
- **ao, J.; Zhang, S.; Liu, Q.; Xu, T.; Zhang, X. Microfluidic-based plasmonic microneedle biosensor for uric acid ultrasensitive monitoring. Sens. Actuators B Chem. 2024, 398, 134685. [Google Scholar] [CrossRef]
- Zheng, L.; Zhu, D.; **ao, Y.; Zheng, X.; Chen, P. Microneedle coupled epidermal sensor for multiplexed electrochemical detection of kidney disease biomarkers. Biosens. Bioelectron. 2023, 237, 115506. [Google Scholar] [CrossRef]
- He, Q.-Y.; Zhao, J.-H.; Du, S.-M.; Li, D.-G.; Luo, Z.-W.; You, X.-Q.; Liu, J. Reverse iontophoresis generated by porous microneedles produces an electroosmotic flow for glucose determination. Talanta 2024, 267, 125156. [Google Scholar] [CrossRef]
- Huang, H.; Qu, M.; Zhou, Y.; Cao, W.; Huang, X.; Sun, J.; Sun, W.; Zhou, X.; Xu, M.; Jiang, X. A microneedle patch for breast cancer screening via minimally invasive interstitial fluid sampling. Chem. Eng. J. 2023, 472, 145036. [Google Scholar] [CrossRef]
- Park, W.; Maeng, S.-W.; Mok, J.W.; Choi, M.; Cha, H.J.; Joo, C.-K.; Hahn, S.K. Hydrogel Microneedles Extracting Exosomes for Early Detection of Colorectal Cancer. Biomacromolecules 2023, 24, 1445–1452. [Google Scholar] [CrossRef]
- Abd-El-Azim, H.; Tekko, I.A.; Ali, A.; Ramadan, A.; Nafee, N.; Khalafallah, N.; Rahman, T.; Mcdaid, W.; Aly, R.G.; Vora, L.K.; et al. Hollow microneedle assisted intradermal delivery of hypericin lipid nanocapsules with light enabled photodynamic therapy against skin cancer. J. Control. Release 2022, 348, 849–869. [Google Scholar] [CrossRef] [PubMed]
- Ma, Y.; Liu, Y.; Wang, Y.; Gao, P. Transdermal codelivery system of resveratrol nanocrystals and fluorouracil@ HP-β-CD by dissolving microneedles for cutaneous melanoma treatment. J. Drug Deliv. Sci. Technol. 2024, 91, 105257. [Google Scholar] [CrossRef]
- Xu, R.; Guo, H.; Chen, X.; Xu, J.; Gong, Y.; Cao, P.; Wei, C.; **ao, F.; Wu, D.; Chen, W.; et al. Smart hydrothermally responsive microneedle for topical tumor treatment. J. Control. Release 2023, 358, 566–578. [Google Scholar] [CrossRef]
Type of Microneedles | Delivery Strategies | Applications | References |
---|---|---|---|
Solid | The poke-and-patch method involves the application of numerous microneedles to create pores as a preparatory step. Following this, a traditional drug formulation is applied to the skin surface. | Skin pre-treatment for the delivery of potassium chloride, insulin, vaccines, cosmetics, and antipsychotic medication; monitoring of glucose and lactate levels; urea sensing. | [31,32,33,34,35,36,37] |
Coated | The coat-and-poke technique involves applying a water-soluble drug coating on solid microneedles. This coating dissolves during administration, depositing the drug directly into the skin. | Delivery of proteins, vaccines, parathyroid hormone, insulin, desmopressin, and dexamethasone; sampling, isolation, and identification of biomarkers; monitoring of glucose. | [38,39,40,41,42,43,44,45] |
Dissolving | The poke-and-dissolve method utilizes biodegradable or water-soluble microneedles encapsulating drugs. These microneedles dissolve upon application, releasing their therapeutic payload into the skin. | Delivery of vitamin B12, vaccines, therapeutic peptides, adenosine, doxorubicin, triamcinolone acetonide, near-IR photosensitizer (Redaporfin™), genes, and sodium nitroprusside in combination with sodium thiosulfate, tofacitinib, flurbiprofen axetil, epidermal growth factor, and ascorbic acid. | [46,47,48,49,50,51,52,53,54,55,56,57,58,59,60,61] |
Hollow | The poke-and-flow method involves microneedles with a hole in the center or side of their structure, allowing the drug to flow across the skin. | Delivery of teriflunomide, ceftriaxone sodium, mRNA, and vaccines; cell therapy; monitoring of glucose; synthetic amphetamine-type substance sensing; dermal interstitial fluid sampling and sensing. | [62,63,64,65,66,67,68,69] |
Hydrogel-forming | The poke-and-release method utilizes water-insoluble microneedles injected into the skin, gradually releasing the encapsulated therapeutic molecule. The patch remains on the skin after application. | Delivery of albendazole, sildenafil citrate, metformin hydrochloride, methotrexate, and tuberculosis drugs; dermal interstitial fluid sampling. | [70,71,72,73,74,75] |
Materials | Advantages | Limitations | References |
---|---|---|---|
Maltose | Biocompatible; No dermatological issues were noted on the human skin following insertion; High mechanical strength; Easy degradation; Fast dissolution; Controllable viscosity; Drug stability enhancer; Efficiently deliver protein drugs; Accelerate drug delivery. | High melting point is unfavorable for heat-sensitive drugs; The use of microneedles in a humid environment is limited due to the poor moisture resistance. | [95,96,97,98] |
Hyaluronic acid (HA) | FDA-approved; Biocompatible; Biodegradable; Water solubility; Faster rate of dissolving; Enhance mechanical strength of dissolving microneedles; Quickly release drugs; Nontoxic and non-irritant; HA can be utilized for extended durations; No hypersensitivity effects or side effects associated with HA microneedles were identified in clinical studies. | Poor moisture resistance; Easy to shrink after microneedle fabrication. | [51,99,100,101,102,103] |
2-Hydroxypropyl-β-cyclodextrin (HP-β-CD) | Improve the solubility of poorly water-soluble drugs by forming inclusion compounds; Enhance mechanical strength of dissolving microneedles. | Selective inclusion. | [51,99,104] |
Carboxymethylcellulose (CMC) | FDA-approved; Biocompatible; Biodegradable; Dissolve quickly in water; Can achieve slow and controllable release of drugs; In vitro cytotoxicity analysis and in vivo tissue response test did not show any side effects after treatment with CMC microneedles. | Poor moisture resistance; Poor mechanical strength. | [91,105,106] |
Chitosan | Biocompatible, biodegradable, and nontoxic; It can either be cleared by the kidneys in vivo or degraded into fragments that are subsequently cleared by the kidneys; Antibacterial properties; Sufficient mechanical strength to penetrate porcine cadaver skin; Strong adsorption ability. | Limited raw materials; Negative water solubility. | [107,108,109,110,111] |
Starch | Non-cytotoxic; Biodegradable; Higher mechanical strength than CMC. | Pure starch is more rigid and prone to fracturing and exhibits inferior film-forming characteristics. | [112,113,114] |
Gelatin | Excellent biodegradability, biocompatibility, film formation, gelation, emulsification, water retention, and drug loading ability; Provides high safety and slow release. | Toughness of gelatin is poor, and it is easy to fracture; Low melting point and poor stability. | [107,112] |
Silk fibroin | FDA-approved biomaterial; Non-cytotoxic, biocompatible, and the in vivo degradation products are non-inflammatory; Adequate mechanical force to pierce mouse skin for drug delivery; High tensile strength and toughness; Excellent mechanical characteristics, efficient gradual release of drugs, and favorable processing conditions. | Long fabrication time. | [115,116,117,118,119,120] |
Poly(vinylpyrrolidone)(PVP) | Sufficient strength to pierce mouse skin; Enables the avoidance of organic solvents and high temperatures, aiding in the preservation of the drug’s stability and efficacy; Biocompatible and biodegradable; Low oral and transdermal toxicity; Non-irritating to skin; No adverse effects related to treatment were observed in a 6-month study. | Poor moisture resistance. | [112,121,122,123,124,125] |
Polyvinyl alcohol (PVA) | Sufficient strength to penetrate both porcine cadaver skin and mouse skin; FDA-approved material; Biocompatible; Biodegradable; Good viscosity and toughness; Low cytotoxicity; Dissolve quickly in water. | Poor moisture resistance. | [107,126,127,128] |
Polylactic acid (PLA) | FDA-approved biomaterial for the use of implants in humans; Biocompatible; Biodegradable; The in vivo degradation products are nontoxic; Excellent mechanical strength; High modulus of elasticity. | Fabrication of microneedles typically necessitates high temperatures (exceeding 170 °C) or organic solvents. | [31,107,129] |
Polyglycolic acid (PGA) | FDA-approved biomaterial; Biocompatible; Biodegradable; The in vivo degradation products are nontoxic; Excellent mechanical strength to penetrate the regenerated human skin. | Fabrication of microneedles typically necessitates high temperatures or organic solvents. | [130] |
Poly(lactide-co-glycolic acid) (PLGA) | Outstanding mechanical strength to pierce the murine skin; FDA-approved biomaterial; Biocompatible; Biodegradable; The in vivo degradation products are nontoxic. | Fabrication of microneedles typically necessitates high temperatures or organic solvents. | [129,131,132] |
Polycaprolactone (PCL) | FDA-approved biomaterial; Biocompatible; Biodegradable; Non-cytotoxic; The in vivo degradation products are nontoxic; Sufficient mechanical strength to penetrate porcine cadaver skin for drug delivery. | The processing temperature is comparatively lower than PLA, PGA, and PLGA, yet still above 50 °C, which poses a constraint on incorporating heat-sensitive drugs such as insulin. | [129,133] |
Fabrication Method | Advantages | Limitations | References |
---|---|---|---|
MEMS-based methods | Very precise geometries; Smooth vertical sidewall. | Time consuming; Expensive; Difficult to fabricate complex structures; Basic material limited to silicone and photocurable polymers. | [165,166] |
Micromolding | High precision; Cost effective; Used for mass production; A large variety of basic material. | Difficult to fabricate complex structures; Drug load capacity; Mechanical behavior; Controls the depth of penetration. | [165,166] |
Laser ablation | Less time consuming. | Might cause a crack or fatigue resistance on the substrate (microneedle array); Expensive; Not suitable for large fabrication. | [166] |
Injection molding | Mass production; Cost effective. | High initial cost (machine equipment cost); Complex process. | [166] |
Method | Advantages | Disadvantages |
---|---|---|
Mechanical force drawing | Cost effective | Time consuming Low precision Unable to produce complex structures Restricted to thermoplastic materials |
Contact drawing | Cost effective Rapid | Low precision Unable to produce complex structures Viscosity of basic material requires adjustment |
Electro-drawing | Cost effective Rapid | Low precision Unable to produce complex structures Conductivity of basic material requires adjustment |
Centrifugal drawing | Cost effective Rapid | Low precision Unable to produce complex structures |
Method | Advantages | Disadvantages |
---|---|---|
Fused deposition modelling (FDM) | Cost effective Less time consuming | Low precision Cannot fabricate complex structures Needs post treatment |
Stereolithography (SLA) | Less time consuming Able to fabricate complex structures | Average precision |
Two-photon polymerization (2PP) | High precision Easy to fabricate complex structures | Expensive Time consuming Difficult to fabricate objects with large volume |
Microneedle System | Active Ingredient/Sampling | Application | Reference |
---|---|---|---|
Polymeric microneedles | Ovalbumin and CpG | Vaccine delivery | [285] |
Hollow microneedles | Insulin | Vaccine delivery | [310] |
Dissolving microneedle patches | Heat-inactivated bacteria | Vaccine delivery | [311] |
Solid pyramidal microneedle | Stabilized HIV envelope trimer immunogen and adjuvant | Vaccine delivery | [312] |
Microneedle patches | Acetyl-hexapeptide-3 | Wrinkle | [280] |
Stainless solid microneedles | 5-Fluorouracil | Keloids | [313] |
Poly(ionic liquid)-based microneedle patches | Salicylic acid | Acne | [314] |
Dissolvable hyaluronic acid microneedles | Shikonin | Hypertrophic scars | [315] |
Methacrylate gelatin/polyethylene glycol diacrylate double-network hydrogel microneedle patch | Betamethasone | Hypertrophic scars | [316] |
Dissolving microneedle array | MiRNA-modified functional exosomes | Hypertrophic scars | [317] |
Dissolving gelatin and starch microneedle patches | Losartan | Hypertrophic scars | [318] |
Dissolving microneedle | Triamcinolone acetonide | Psoriasis | [50] |
Dissolving microneedle patches | Tetramethylpyrazine | Rheumatoid arthritis | [319] |
Hydrogen peroxide-responsive microneedle | Integrin αvβ6-blocking antibody | Pulmonary fibrosis | [320] |
Dissolvable microneedles | Dexamethasone | Atopic dermatitis | [321] |
Natural antimicrobial material microneedles | Peony leaf extract | Chronic wounds | [322] |
Hyaluronic acid microneedle | Recombinant humanized collagen type III and naproxen loaded poly(lactic-co-glycolic acid) nanoparticle | Chronic wounds | [323] |
Zwitterionic microneedle dressings | Zinc oxide nanoparticles and asiaticoside | Chronic wounds | [324] |
Encoded structural color microneedle patches | Photonic crystals | Wound biomarker detection | [325] |
Microneedle patches | Interstitial fluid | Sampling of interstitial fluid | [326] |
Microfluidic-based wearable plasmonic microneedle sensor | Interstitial fluid | Uric acid monitoring | [327] |
Polymeric-microneedle-coupled electrochemical sensor array | Interstitial fluid | Diagnosis of chronic kidney disease | [328] |
Ion-conductive porous microneedle-based glucose sensing device combined with reverse ion electroosmosis | Interstitial fluid | Glucose determination (management of chronic diseases) | [329] |
Gelatin methacrylate–acrylic acid microneedle patch | Interstitial fluid | Breast cancer screening | [330] |
Hydrogel microneedles | Interstitial fluid | Colorectal cancer diagnosis | [331] |
AdminPen™ hollow microneedle array | Hypericin lipid nanocapsules | Non-melanoma skin cancer | [332] |
Dissolvable microneedle patch | Resveratrol nanocrystals and fluorouracil@hydroxypropyl-beta-cyclodextrin | Cutaneous melanoma | [333] |
Hydrothermally responsive multi-round acturable microneedle | Docetaxel | Subcutaneous tumors | [334] |
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© 2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Oliveira, C.; Teixeira, J.A.; Oliveira, N.; Ferreira, S.; Botelho, C.M. Microneedles’ Device: Design, Fabrication, and Applications. Macromol 2024, 4, 320-355. https://doi.org/10.3390/macromol4020019
Oliveira C, Teixeira JA, Oliveira N, Ferreira S, Botelho CM. Microneedles’ Device: Design, Fabrication, and Applications. Macromol. 2024; 4(2):320-355. https://doi.org/10.3390/macromol4020019
Chicago/Turabian StyleOliveira, Cristiana, José A. Teixeira, Nelson Oliveira, Sónia Ferreira, and Cláudia M. Botelho. 2024. "Microneedles’ Device: Design, Fabrication, and Applications" Macromol 4, no. 2: 320-355. https://doi.org/10.3390/macromol4020019