Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons
Abstract
:1. Introduction
2. Results
2.1. Ex Vivo Results
2.2. Histomorphometric Results
3. Discussion
4. Materials and Methods
4.1. Keratose-Coated Balloons
4.2. Peripheral-Simulating Bioreactor
4.3. Ex Vivo DCB Testing and Arterial Time Drug Concentration
4.4. Rabbit Injury Model
4.5. Arterial Sections
4.6. Histomorphometric Analysis
4.7. Statistical Analysis
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Sample Availability: Samples of the compounds are not available from the authors. |
KOS-PXL | Commercial DCB | p Value | |
---|---|---|---|
Time Points | ng/mg | ng/mg | |
1 h (pulse only) | 41.01 ± 32.11 | 82.88 ± 31.81 | 0.30 |
3 day (pulse only) | 17.56 ± 7.19 | 24.44 ± 27.03 | 0.96 |
3 day (pulse + vascular motion) | 14.89 ± 4.12 | 0.60 ± 0.26 | 0.018 |
No Coating | KOS-only | PXL-only | KTO-PXL | p Value | |
---|---|---|---|---|---|
Morphometric Measurements | |||||
EEL, mm2 | 1.87 ± 0.33 | 1.64 ± 0.63 | 1.98 ± 0.48 | 1.39 ± 0.39 | 0.37 |
IEL, mm2 | 1.32 ± 0.24 | 1.15 ± 0.55 | 1.58 ± 0.24 | 0.99 ± 0.45 | 0.52 |
Lumen, mm2 | 1.18 ± 0.24 | 1.00 ± 0.55 | 1.32 ± 0.30 | 0.92 ± 0.43 | 0.58 |
Media, mm2 | 0.55 ± 0.10 | 0.50 ± 0.11 | 0.59 ± 0.18 | 0.40 ± 0.08 | 0.21 |
Neointimal area, mm2 | 0.15 ± 0.06 | 0.14 ± 0.04 | 0.11 ± 0.05 | 0.06 ± 0.02 | 0.085 |
Neointimal thickness, mm | 0.10 ± 0.011 | 0.069 ± 0.022 | 0.066 ± 0.018 | 0.053 ± 0.003 | 0.005 |
Percent area stenosis, % | 10.88 ± 4.52 | 9.99 ± 3.78 | 7.92 ± 3.84 | 6.80 ± 2.74 | 0.45 |
Histological Analysis | |||||
Injury | 1.00 ± 0.41 | 0.75 ± 1.19 | 1.13 ± 1.32 | 0.50 ± 0.41 | 0.74 |
EC Score | 0.25 ± 0.50 | 0.00 ± 0.00 | 0.25 ± 0.50 | 1.50 ± 0.58 | 0.013 |
Inflammation | 0.25 ± 0.50 | 0.00 ± 0.00 | 0.50 ± 0.58 | 0.25 ± 0.50 | 0.86 |
SMC Loss | 0.00 ± 0.00 | 0.00 ± 0.00 | 0.25 ± 0.50 | 1.00 ± 0.82 | 0.081 |
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Goel, E.; Erwin, M.; Cawthon, C.V.; Schaff, C.; Fedor, N.; Rayl, T.; Wilson, O.; Christians, U.; Register, T.C.; Geary, R.L.; et al. Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons. Molecules 2020, 25, 1596. https://doi.org/10.3390/molecules25071596
Goel E, Erwin M, Cawthon CV, Schaff C, Fedor N, Rayl T, Wilson O, Christians U, Register TC, Geary RL, et al. Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons. Molecules. 2020; 25(7):1596. https://doi.org/10.3390/molecules25071596
Chicago/Turabian StyleGoel, Emily, Megan Erwin, Claire V. Cawthon, Carson Schaff, Nathaniel Fedor, Trevor Rayl, Onree Wilson, Uwe Christians, Thomas C. Register, Randolph L. Geary, and et al. 2020. "Pre-Clinical Investigation of Keratose as an Excipient of Drug Coated Balloons" Molecules 25, no. 7: 1596. https://doi.org/10.3390/molecules25071596