Microneedle-Based Delivery: An Overview of Current Applications and Trends
Abstract
:1. Introduction
2. Microneedle-Based Transdermal Delivery Approaches
2.1. Solid Microneedles for “Poke and Patch”
2.2. Coated Microneedles for “Coat and Poke”
2.3. Dissolving and Hydrogel-Forming Microneedles for “Poke and Release”.
2.4. Hollow Microneedles for “Poke and Flow”
3. MNA Fabrication
3.1. Materials
3.2. Manufacturing Processes
4. Applications in Drug and Vaccine Delivery
4.1. Immunization
4.2. Therapy
4.2.1. Therapeutic Proteins
4.2.2. Insulin
4.2.3. Vitamins
4.2.4. Antibiotics
4.2.5. Natural Compounds
4.3. Cosmeceuticals
5. Use of MNA in Other Organs, Stimuli Responsive MNA, and Delivery of Cells
6. Safety Considerations
6.1. Pain
6.2. Infections
6.3. Biocompatibility, Immunogenicity, and Local Skin Reactions
7. Conclusions
Author Contributions
Funding
Acknowledgments
Conflicts of Interest
References
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Method | Advantages | Disadvantages | Ref. |
---|---|---|---|
Chemical enhancers | High effectiveness in combination with small molecules | Poor effectiveness in combination with macromolecules and hydrophilic molecules Inability to locate the effects on the stratum corneum (SC) Skin reactions (irritation, inflammation, erythema) Anti-inflammatory, anti-irritation pre-treatments are recommended | [26,27,28] |
Microsystems and nanosystems | Possibility to localize the effects and drug release in the first layers of the skin | Large size can hinder the penetration of the system into the skin | [29] |
Prodrugs | Improve chemical stability Avoiding skin reactions | Large size can hinder the diffusion through the skin | [30] |
Iontophoresis | Rapidly responsive molecular transport Control of transport magnitude | Devices are expensive Not applicable for long periods of time due to the polarization of the skin Inability to locate the effects on the SC Skin reactions (irritation, inflammation, erythema) | [31,32,33,34,35] |
Electroporation | Rapidly responsive molecular transport Control of transport magnitude | Devices are expensive Inability to locate the effects on the SC Skin reactions (irritation, inflammation, erythema) | [36,37] |
Sonophoresis | Rapidly responsive molecular transport Control of transport magnitude Good effectiveness in combination with hydrophilic drugs and medium-large molecular weight | Devices are expensive Poor range of molecules administered safely Inability to locate the effects on the SC Skin reactions (irritation, inflammation, erythema) | [38,39,40,41] |
Thermal methods | Possibility to diffuse large-size molecules | Inability to locate the effects on the SC Intense skin reactions (irritation, inflammation, erythema) | [42,43] |
Jet injectors | Delivery of solid particles or liquids Possibility to control de depth where the drug is deposited Useful for vaccination | Not applicable for long periods of time Possibility of contamination of the devices with interstitial fluids | [44,45,46,47] |
Material | MNA Type | Fabrication Process | Advantages | Disadvantages | Ref. |
---|---|---|---|---|---|
Stainless steel, Titanium, Nickel, Gold | Solid, Hollow, Coated (array) | Laser cutting, laser ablation, etching, electropolishing, lithography, and microstereolithography | Desirable mechanical properties and high tensile strength | Fractures, corrosion, and poor biocompatibility of some metals | [78,79,80,81,82,83,84] |
Alumina, Zirconia, Calcium phosphate/sulphate | Ceramic | Lithography and ceramic sintering | Good biocompatibility | Fractures | [85,86,87,88] |
Silicon | Solid, Hollow, Coated (array) | Etching, Lithography | Desirable mechanical properties | High material cost, long fabrication, and fractures | [89,90,91,92] |
Borosilicates (glass) | Hollow | Pulling pipettes | Good biocompatibility | Fractures | [75,93,94,95] |
Sugars | Solid, Dissolving | Solvent casting or micromolding | Good biocompatibility | Mechanical properties are more difficult to achieve, stability problems, storage issues. | [96,97,98,99] |
Polymers | Dissolving, Hydrogel-forming, Coated (coating) | Solvent casting or micromolding | Optimal biocompatibility, biodegradation, and absence of waste after use | Mechanical properties are more difficult to achieve | [69,100,101,102,103,104,105,106,107,108,109] |
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Guillot, A.J.; Cordeiro, A.S.; Donnelly, R.F.; Montesinos, M.C.; Garrigues, T.M.; Melero, A. Microneedle-Based Delivery: An Overview of Current Applications and Trends. Pharmaceutics 2020, 12, 569. https://doi.org/10.3390/pharmaceutics12060569
Guillot AJ, Cordeiro AS, Donnelly RF, Montesinos MC, Garrigues TM, Melero A. Microneedle-Based Delivery: An Overview of Current Applications and Trends. Pharmaceutics. 2020; 12(6):569. https://doi.org/10.3390/pharmaceutics12060569
Chicago/Turabian StyleGuillot, Antonio José, Ana Sara Cordeiro, Ryan F. Donnelly, M. Carmen Montesinos, Teresa M. Garrigues, and Ana Melero. 2020. "Microneedle-Based Delivery: An Overview of Current Applications and Trends" Pharmaceutics 12, no. 6: 569. https://doi.org/10.3390/pharmaceutics12060569