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
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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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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