Method for increasing the permeability of an epithelial barrier
View Patent ↗Disclosed are nanotopography-based methods and devices for interacting with a component of epithelial tissue and increasing the permeability of the tissue. Devices include structures fabricated on a surface to form a nanotopography. A random or non-random pattern of structures may be fabricated such as a complex pattern including structures of differing sizes and/or shapes. Microneedles may be beneficially utilized for delivery of an agent to a cell or tissue. Devices may be utilized to directly or indirectly alter cell behavior through the interaction of a fabricated nanotopography with the components of epithelial tissue.
1. A method for increasing the permeability of a cellular layer that comprises epithelial cells, the method comprising:
contacting the cellular layer with a microneedle, the microneedle including a plurality of nanostructures and microstructures formed on an external surface thereof in a predetermined pattern, wherein at least a portion of the microstructures have a cross-sectional dimension of greater than about 500 nanometers and less than about 10 micrometers and a height of from about 20 nanometers to about 1 micrometer, the cross-sectional dimension of the microstructures being greater than the height of the microstructures, wherein at least a portion of the nanostructures having a cross-sectional dimension of from about 5 nanometers to about 500 nanometers, wherein subsequent to contact between the cellular layer and the microneedle, the cellular layer exhibits increased permeability to the drug compound.
2. The method according to claim 1 , wherein subsequent to contact between the cellular layer and the microneedle, the transepithelial electrical resistance of the cellular layer is less than about 95% of the transepithelial electrical resistance of the layer prior to contact with the microneedle.
3. The method according to claim 1 , wherein subsequent to the contact between the cellular layer and the microneedle, the transepithelial electrical resistance of the cellular layer is less than about 85%, of the transepithelial electrical resistance of the layer prior to contact with the microneedle.
4. The method according to claim 1 , wherein subsequent to the contact between the cellular layer and the microneedle, the transepithelial electrical resistance of the cellular layer is less than about 70% of the transepithelial electrical resistance of the layer prior to contact with the microneedle.
5. The medical device of claim 1 , further comprising second nanostructures having a cross-sectional dimension less than the cross-sectional dimension of the microstructures and greater than the cross-sectional dimension of the plurality of nanostructures.
6. The method according to claim 1 , wherein the cellular layer is skin.
7. The method according to claim 1 , the method changing the structure of an intercellular junction.
8. The method according to claim 7 , wherein the intercellular junction is a tight junction.
9. The method according to claim 1 , wherein the microneedle contains a channel that is in fluid communication with a drug compound.
10. The method according to claim 9 , wherein the drug compound is a protein therapeutic.
11. The method according to claim 10 , wherein the drug compound has a molecular weight greater than about 100 kDa.
12. The method according to claim 9 , wherein the drug compound is delivered by the microneedle and permeates across the cellular layer via paracellular transport.
13. The method according to claim 9 , wherein the drug compound is delivered by the microneedle and permeates across the cellular layer via transcellular transport.
14. The method according to claim 9 , wherein drug compound is held within a reservoir.
15. The method according to claim 1 , wherein at least a portion of the nanostructures have an aspect ratio of from about 0.2 to about 5.
16. The method according to claim 1 , wherein the pattern has a fractal dimension of greater than about 1.
17. The method according to claim 1 , wherein at least a portion of the nanostructures have a cross-sectional dimension of from about 100 to about 300 nanometers.
18. The method according to claim 1 , wherein the nanostructures have approximately the same cross-sectional dimension.
19. The method according to claim 1 , wherein at least a portion of the nanostructures have a center-to-center spacing of from about 50 nanometers to about 1 micrometer.
20. The method according to claim 1 , wherein the ratio of the cross sectional dimension of two adjacent nanostructures to the center-to-center spacing between those two structures is between about 1:1 and about 1:4.
21. The method according to claim 1 , wherein at least a portion of the nanostructures have an equidistant spacing.
22. The method according to claim 1 , wherein at least a portion of the nanostructures have a height of from about 10 nanometers to about micrometer.
23. The method according to claim 1 wherein at least a portion of the nanostructures have an aspect ratio of from about 0.5 to about 3.5.
24. The method according to claim 9 , wherein the drug compound is a TNF-α blocker.
25. The method according to claim 1 , wherein the microneedle contains a channel for delivering the drug compound.
26. The method according to claim 1 , wherein at least a portion of the nanostructures have a cross-sectional dimension of from about 20 to about 400 nanometers and at least a portion of the microstructures have a cross-sectional dimension of from about 600 nanometers to about 1.5 micrometers.
27. The method according to claim 1 , wherein at least a portion of the nanostructures have a height greater than a cross-sectional dimension.
28. The method according to claim 1 , wherein at least a portion of the nanostructures are in the form of pillars.