Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin
Abstract
:1. Introduction
2. Materials and Methods
2.1. Materials
2.2. Human Skin
2.3. Production of Dissolving Microneedle Arrays
2.4. Microneedle Arrays
2.5. Applicator Design
2.6. Pressing Force and Impact Insertion Application
2.7. Microneedle Applicator Controller
2.8. Force Calibration for Pressing Force Application
2.9. Calibration of Impact Velocity for Impact Insertion
2.10. Influence of the Applicator’s Angle as a Function of the Pulse Width
2.11. Application of MNAs onto Ex Vivo Human Skin
2.12. Determination of Penetration Efficiency by a Trypan Blue Assay
2.13. Calculation of Penetration Parameters
2.14. Normalization of Penetration Efficiency
2.15. Delivery of Fluorescently Labeled Ovalbumin into Pierced Skin
3. Results
3.1. Microneedles Appearance
3.2. Applicator Setting: Velocity
3.3. Calibration of Applicator
3.4. Influence of the Applicator’s Angle on the Impact Velocity
3.5. Penetration of Human Skin by Pressing Force and Impact Application
3.6. Calculation of Penetration Parameters
3.7. Relation between Penetration Efficiency and Antigen Dose Delivered into the Skin
4. Discussions
4.1. Microneedle Applicator
4.2. Skin Penetration by Microneedles
4.3. Delivery of a Model Antigen in Relation with the Penetration Efficiency
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Microneedle Array | Material | Array Geometry | Microneedle Length (µm) | Microneedle Density (cm−1) | Backplate Surface (mm2) | Number of MNs |
---|---|---|---|---|---|---|
Bosch | Silicon | Square (5 × 5 mm) | 320 | 2304 | 25 | 576 |
MLT-475 | Ceramic | Circular (d = 9 mm) | 475 | 150 | 69 | 105 |
MLT-200 | Ceramic | Circular (d = 9 mm) | 200 | 600 | 69 | 414 |
Tyndall | Silicon | Square (5 × 5 mm) | 300 | 64 | 25 | 16 |
dMNA | Hyaluronan | Square (5 × 5 mm) | 300 | 64 | 25 | 16 |
dMNA-BP | Hyaluronan | Square (5 × 5 mm) | 300 | 64 | 25 | 16 |
Bosch | MLT-200 | MLT-475 | Tyndall | dMNA | dMNA-BP | |
---|---|---|---|---|---|---|
Tip diameter (µm) | 1.2 ± 0.3 | 7.5 ± 1.0 | 7.6 ± 0.9 | 3.8 ± 0.4 | 4.3 ± 0.7 | 4.0 ± 0.3 |
Pulse Width (8 Bit Value) | Impact Velocity (cm/s) | Impact Energy (mJ) |
---|---|---|
90 | 27.40 | 0.94 |
104 | 42.50 | 2.16 |
136 | 70.60 | 6.06 |
174 | 97.40 | 11.85 |
221 | 125.70 | 19.43 |
250 | 138.10 | 23.84 |
Reproducibility of Skin Piercing | Bosch (300 µm) | MLT-475 (475 µm) | MLT-200 (200 µm) | Tyndall (300 µm) | dMNA (300 µm) | dMNA-BP (300 µm) |
---|---|---|---|---|---|---|
RSD (%) (125–138 cm/s) | 1 | 6 | 25 | 2 | 4 | 2 |
RSD (%) (17–25 N) | 9 | 42 | 121 | 9 | 16 | 7 |
Microneedle Array | Impact Energy Per: | Pressing Force Per: | ||||
---|---|---|---|---|---|---|
MNA (mJ) | Individual MN (mJ) | mm2 (mJ) | MNA (N) | Individual MN (mN) | mm2 (mN) | |
Bosch (300 µm) | 0.97 | 0.002 | 0.04 | 1.4 | 2.4 | 56.0 |
MLT-475 (475 µm) | 5.47 | 0.052 | 0.08 | 6.3 | 59.8 | 91.4 |
MLT-200 (200 µm) | 21.85 | 0.053 | 0.31 | >25.0 * | >60.1 * | >360.2 * |
Tyndall (300 µm) | <1.00 * | <0.063 | <0.04 | <1.0 * | <62.5 * | <40.0 * |
dMNA (300 µm) | 1.28 | 0.080 | 0.05 | <1.0 * | <62.5 * | <40.0 * |
dMNA-BP (300 µm) | <1.00 * | <0.063 | <0.04 | <1.0 * | <62.5 * | <40.0 * |
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Leone, M.; Van Oorschot, B.H.; Nejadnik, M.R.; Bocchino, A.; Rosato, M.; Kersten, G.; O’Mahony, C.; Bouwstra, J.; Van der Maaden, K. Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin. Pharmaceutics 2018, 10, 211. https://doi.org/10.3390/pharmaceutics10040211
Leone M, Van Oorschot BH, Nejadnik MR, Bocchino A, Rosato M, Kersten G, O’Mahony C, Bouwstra J, Van der Maaden K. Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin. Pharmaceutics. 2018; 10(4):211. https://doi.org/10.3390/pharmaceutics10040211
Chicago/Turabian StyleLeone, Mara, Bart H. Van Oorschot, M. Reza Nejadnik, Andrea Bocchino, Matteo Rosato, Gideon Kersten, Conor O’Mahony, Joke Bouwstra, and Koen Van der Maaden. 2018. "Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin" Pharmaceutics 10, no. 4: 211. https://doi.org/10.3390/pharmaceutics10040211
APA StyleLeone, M., Van Oorschot, B. H., Nejadnik, M. R., Bocchino, A., Rosato, M., Kersten, G., O’Mahony, C., Bouwstra, J., & Van der Maaden, K. (2018). Universal Applicator for Digitally-Controlled Pressing Force and Impact Velocity Insertion of Microneedles into Skin. Pharmaceutics, 10(4), 211. https://doi.org/10.3390/pharmaceutics10040211