Polymeric Microneedles: An Emerging Paradigm for Advanced Biomedical Applications
Abstract
:1. Introduction
2. Types of Microneedles
2.1. Solid Microneedles
2.2. Hollow Microneedle
2.3. Coated Microneedles
2.4. Dissolving Microneedles
2.5. Hydrogel Microneedles
3. Polymeric Microneedle Technology
3.1. Classification of Polymer Used for Microneedle Fabrication
3.1.1. Dextran
3.1.2. Hyaluronic Acid
3.1.3. Chitin and Chitosan
3.1.4. Alginate
3.1.5. Gelatin
3.1.6. Gantrez
3.1.7. Hydroxypropyl Methylcellulose (HPMC)
3.1.8. Polycigycidyl Methacrylate
3.1.9. Polyvinyl Alcohol (PVA)
3.1.10. Polystyrene-Block-Poly-(Acrylic Acid) (PSPAA)
3.1.11. Polylactic Acid (PLA)
3.1.12. Polymethyl Methacrylate (PMMA)
3.1.13. Polystyrene
3.1.14. Polycaprolactone
4. Fabrication Techniques of Microneedles
4.1. Micromolding
4.2. Micromilling
4.3. Atomized Spraying to Fill Molds
4.4. 3D and 4D Printing
4.5. Laser Ablation
4.6. Photolithography
4.7. Printing Techniques
4.8. Etching
4.9. Electrospinning
4.10. Co-Extrusion
5. Biomedical Applications of Polymeric Microneedles
5.1. Therapeutic Applications
5.1.1. Rheumatoid Arthritis
5.1.2. Skin Diseases
Melasma
Psoriasis
5.1.3. Cancer
5.1.4. Diabetes and Obesity
5.2. Drug Delivery
5.2.1. Transdermal
5.2.2. Intraocular
5.3. Diagnostic and Biosensing Applications
5.4. Vaccination
6. Regulatory Considerations and Patent Scenario
7. Conclusions and Future Perspective
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Factor Affecting MN Fabrication | Practical Parameters | Practical Considerations | References |
---|---|---|---|
Material properties | Mechanical properties (stiffness, strength, and toughness). | High stiffness and strength may cause materials to be more difficult to be molded or etched, while materials that are too brittle may be prone to breakage. | [74] |
Chemical properties (reactivity, solubility, and stability). | Highly reactive or unstable materials may require specialized handling or storage conditions. | [75] | |
Biocompatibility (non-toxic, non-immunogenic, and non-inflammatory). | Material should be biocompatible for clinical or medical use. | [76] | |
Compatibility with drug formulations (physical, chemical, and biological interactions). | The material should not adsorb or absorb the drug to avoid any loss of drug efficacy. | [77] | |
Device design | Needle length and diameter. | The length and diameter of the MNs should be optimized for the intended application, taking into account factors such as skin thickness and drug delivery requirements. | [78] |
Needle shape and geometry. | The shape and geometry of the MNs can affect their mechanical properties and ability to penetrate the skin. | [79] | |
Delivery target. | Design considerations shall take into account the target site (depth of penetration topical or deeper penetration), and whether it is a local or systemic action/sensing. | ||
Quality control | Inspection and testing. | Inspected and tested to ensure they meet quality standards and specifications (device dimensions, insertion force, insertion depth, failure force, skin irritation, skin permeation, payload release, lubrication, flexibility, shelf life, etc.) | [9] |
Precision and accuracy of alignment. | Alignment and registration of MNs are important for ensuring consistent performance and drug delivery. | ||
Cost | Materials and manufacturing costs. Ease of fabrication. | Materials should be economic. The material should be easy to fabricate using the chosen manufacturing technique. | [80] |
Regulatory requirements | FDA and other regulatory requirements. | MNs may be subject to regulatory requirements, such as safety and efficacy testing, before they can be approved for use. | [81] |
Method of MN Fabrication | Precision of Fabrication | Scalability | Ability to Control Shape and Size | Ability to Fabricate Complex Structures and Patterns | Resolution | Cost |
---|---|---|---|---|---|---|
Micromolding | ✓ | ✓ | ✓ | ✓ | ✓ | Low |
Micromilling | ✓ | ✓ | ✓ | ✓ | ✓ | High |
Atomized Spraying to Fill Molds | ✓ | ✓ | ✘ | ✘ | ✓ | Low |
3D Printing | ✓ | ✓ | ✓ | ✓ | ✓ | Low |
Laser Ablation | ✓ | ✘ | ✓ | ✓ | ✓ | High |
Photolithography | ✓ | ✘ | ✓ | ✓ | ✓ | High |
Printing Techniques | ✓ | ✓ | ✓ | ✘ | ✓ | Low |
Etching | ✓ | ✓ | ✓ | ✓ | ✓ | High |
Electrospinning | ✓ | ✓ | ✘ | ✘ | ✓ | High |
Co-Extrusion | ✓ | ✓ | ✓ | ✘ | ✓ | Low |
Additive Fabrication Methods | Materials Used | Type of Microneedles | Layer Resolution | Potential Source | Application | References |
---|---|---|---|---|---|---|
Direct-ink writing (DIW) | Shape memory polymer (SMP) | Solid, hollow | 20–50 µm | Laser beam | Tissue engineering | [90] |
Fused filament fabrication (FFF) | Shape memory hydrogel (SMH) | Coated, hydrogel | 40–70 µm | Laser beam | Prototyping in product development | [91] |
Stereolithography (SLA) | Liquid polymer | Solid, hollow, coated | 50–100 µm | UV light | Anticancer drug delivery | [92] |
Digital light processing (DLP) | Shape memory composite (SMC) | Biodegradable, coated, hydrogel | 25–150 µm | UV light | Transdermal drug delivery | [93] |
Selective laser sintering (SLS) | Liquid crystal elastomer | Solid, biodegradable, hydrogel | 80–90 µm | Laser beam | Disease delivery with medical device | [94] |
Inject method | Shape memory alloy | Biodegradable, solid | 70–100 µm | - | Topical application | [95] |
Polymers | Fabrication Method | Application | References |
---|---|---|---|
Amylopectin | Photolithography | Drug delivery of cosmetics and nutrients | [144] |
Chondroitin sulphate | 2-Photon polymerization (2PP) | Decompressing loaded sodium chondroitin sulphate | [145] |
Carboxy methyl cellulose | 2PP, droplet-born air blowing (DAB) method | To enhance local skin health and rats’ immune function, hair regrowth | [146] |
Dextran | Photon polymerization | Treatment of skin cancer | [16] |
GA lactose | Atomized spraying process | Protein delivery | [147] |
Trehalose | Micromolding | To facilitate peptide delivery | [148] |
Maltose | Atomized spraying process | Drug carrier for anti-cancer agent | [149] |
Fructose | Micromolding | Biosensing | [150] |
Raffinose | Atomized spraying process | Delivery of doxorubicin | [151] |
Thermoplastic starch | Electro-discharge process | Insulin delivery in diabetics | [152] |
Poly-lactic-acid | Fused deposition modelling (FDM), micromolding | Immunization, biosensing | [153] |
Poly-lactic-co-glycolic acid | 2PP, micromolding | Vaccine delivery | [10] |
Polycarbonate PMVEs/MA copolymer | UV lithography, electroforming, laser-based method for micromolding, micromolding | Treatment of poisoning | [154] |
Poly-vinyl-alcohol | Micromolding | Delivery of Nicotinamide Mononucleotide | [155] |
Poly-vinyl-pyrrolidine | 2PP, atomized spraying process | Intradermal drug delivery system, to facilitate peptide delivery | [156] |
Polyglycolic acid | Fused deposition modelling | Vaccination | [14] |
Hyaluronic acid | Micromolding | Treatment of diabetes mellitus, diagnosis | [157] |
Sodium chondroitin | Solvent casting | In topical formulation and local analgesic action | [158] |
Polyethylene glycol | Inject printing | GAP 26 gap junction blocker, biosensor | [159] |
Chitosan | Electrospraying, micromolding | Immunotherapy, provide stability to the antigen used in MN vaccination | [160] |
Polycaprolactone | Printed scaffolds | Cancer therapy | [151] |
Hydroxy propyl methyl cellulose | Atomized spraying to fill molds | Treatment of Alzheimer’s disease | [18] |
Cellulose | --- | Stabilizer and film forming | [159] |
Polysorbate 80 | Inject printing | Used in cardiac disease | [161] |
Polydimethylsiloxane | Mold casting | Cosmetic | [162] |
Polydiacetylenes | Phase inversion | Diagnostic | [163] |
Polycarbonate | Gas pulling | --- | [164] |
Sucrose | --- | Protein stabilizer | [165] |
Chitin | Electrospraying, micromolding | Diagostic tool for tuberculosis | [166] |
Pullulan | Electro-discharge machining process | Deliver protein and peptide-like FITC-BSA | [167] |
Identifier | Starting Year | Clinical Condition | Description | Clinical Trial Phase | References |
---|---|---|---|---|---|
NCT04253418 | 2019 | Sebaceous hyperplasia; skin abnormalities; and skin lesion | Nano-pulse stimulation (NPS) in sebaceous hyperplasia optimization study | N/A | [171] |
NCT04249115 | 2019 | Lesion skin; seborrheic keratosis; skin lesion; and benign skin tumor | Nano-pulse stimulation (NPS) in seborrheic keratosis optimization study | N/A | [171] |
NCT03739398 | 2018 | Wrinkle | A study on the effectiveness and safety evaluation of combination therapy with 1927 nm thulium laser and fractional MN radiofrequency equipment for improvement of skin aging | N/A | [172] |
NCT02745392 | 2016 | Acute migraine | Safety and efficacy of ZP-zolmitriptan intracutaneous MN system for acute treatment of migraine (Zotrip) | Phase 2 Phase 3 | [173] |
NCT03203174 | 2015 | Hyperhidrosis | The use of MN with topical botulinum toxin for treatment of palmer hyperhidrosis | Phase 1 | [174] |
NCT02438423 | 2015 | Influenza | Inactivated influenza vaccine delivered by MN patch or by hypodermic needle | Phase 1 | [175] |
NCT01674621 | 2012 | Post-menopausal osteoporosis | Phase 2 study of BA058 (abaloparatide) TD delivery in postmenopausal women with osteoporosis | Phase 2 | [176] |
NCT01368796 | 2011 | Influenza vaccines | Comparison of 4 influenza vaccines in seniors (PCIRNRT09) | Phase 4 | [177] |
NCT00837512 | 2008 | Type 1 diabetes mellitus | Insulin delivery using MN in type 1 diabetes | Phase 2 Phase 3 | [178] |
US Patent Number | Title | References |
---|---|---|
US10737083B2 | Bioactive components conjugated to dissolvable substrates of MN arrays | [181] |
US10377062B2 | MN arrays formed from polymer films | [182] |
US7429333B2 | Method for fabricating MN array and method for fabricating embossing mold of MN array | [183] |
US10195410B2 | Fabrication process of phase-transition MN patch | [184] |
US9498524B2 | Method of vaccine delivery via MN arrays | [185] |
US9302903B2 | MN devices and production thereof | [186] |
US8708966B2 | MN devices and methods of manufacture and use thereof | [187] |
US8834423B2 | Dissolvable MN arrays for TD delivery to human skin | [188] |
US10682504B2 | MN and method for manufacturing MN | [189] |
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Share and Cite
Kulkarni, D.; Gadade, D.; Chapaitkar, N.; Shelke, S.; Pekamwar, S.; Aher, R.; Ahire, A.; Avhale, M.; Badgule, R.; Bansode, R.; et al. Polymeric Microneedles: An Emerging Paradigm for Advanced Biomedical Applications. Sci. Pharm. 2023, 91, 27. https://doi.org/10.3390/scipharm91020027
Kulkarni D, Gadade D, Chapaitkar N, Shelke S, Pekamwar S, Aher R, Ahire A, Avhale M, Badgule R, Bansode R, et al. Polymeric Microneedles: An Emerging Paradigm for Advanced Biomedical Applications. Scientia Pharmaceutica. 2023; 91(2):27. https://doi.org/10.3390/scipharm91020027
Chicago/Turabian StyleKulkarni, Deepak, Dipak Gadade, Nutan Chapaitkar, Santosh Shelke, Sanjay Pekamwar, Rushikesh Aher, Ankita Ahire, Manjusha Avhale, Rupali Badgule, Radhika Bansode, and et al. 2023. "Polymeric Microneedles: An Emerging Paradigm for Advanced Biomedical Applications" Scientia Pharmaceutica 91, no. 2: 27. https://doi.org/10.3390/scipharm91020027