Polymeric microneedles and rapid additive manufacturing of the same
The invention generally relates to microneedle devices, methods of making same, pharmaceutical compositions comprising same, and methods of treating a disease comprising administering same. Specifically, the disclosed microneedle devices comprise a plurality of biocompatible microneedles having one or more of: (i) a curved, discontinuous, undercut, and/or perforated sidewall; (ii) a sidewall comprising a breakable support; and (iii) a cross-section that is non-circular and non-polygonal. The microneedles may also be tiered. Alternatively, the microneedles may be tiered. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.
1. A method of making a microneedle device, the method comprising the steps of:
(a) providing a build elevator and an optically transparent build surface, wherein the build elevator and the build surface together define a build region there between, wherein the build surface is permeable to a polymerization inhibitor, and wherein the build surface is in fluid communication with a source of the polymerization inhibitor;
(b) filling the build region with a polymerizable liquid;
(c) irradiating the build region through the build surface to produce a solid polymerized region coinciding with a cross-section of the device in the build region;
(d) forming or maintaining a liquid film release layer between the solid polymerized region and the build surface by supplying the polymerization inhibitor thereto, wherein the liquid film release layer comprises the polymerizable liquid, and wherein the polymerization of the polymerizable liquid is inhibited by the polymerization inhibitor at the liquid film release layer; and
(e) advancing the build elevator away from the build surface to create a subsequent build region between the solid polymerized region and the build surface while concurrently filling the subsequent build region with the polymerizable liquid,
wherein steps (c)-(e) are repeated so as to form the device to comprise:
(f) a backing; and
(g) a plurality of biocompatible microneedles projecting from the backing, wherein the microneedles comprise one or more of:
(i) a curved, discontinuous, undercut, or perforated sidewall;
(ii) a sidewall comprising a breakable support; and
(iii) a cross-section that is non-circular and non-polygonal, and/or wherein the microneedles are tiered in addition or in the alternative to (i)-(iii), and
wherein the polymerizable liquid is exchanged with another polymerizable liquid of different polymerizable material prior to at least one instance of said repeating so as to produce multi-component microneedles.
2. The method of claim 1 , wherein said irradiating is via actinic radiation.
3. The method of claim 1 , wherein said advancing comprises moving the build elevator vertically away from the build surface.
4. The method of claim 1 , wherein the microneedle device is formed in less than about 30 minutes.
5. The method of claim 1 , wherein the microneedles comprise a curved, discontinuous, undercut, or perforated sidewall.
6. The method of claim 5 , wherein the microneedles comprise a sidewall comprising a breakable support.
7. The method of claim 5 , wherein the microneedles are tiered.
8. The method of claim 1 , wherein the microneedles comprise an undercut sidewall.
9. The method of claim 8 , wherein the microneedles comprise a sidewall comprising a breakable support.
10. The method of claim 8 , wherein the microneedles are tiered.
11. The method of claim 1 , wherein the microneedles comprise a sidewall comprising a breakable support.
12. The method of claim 11 , wherein the microneedles are tiered.
13. The method of claim 1 , wherein the microneedles comprise a cross-section that is non-circular and non-polygonal.
14. The method of claim 1 , wherein the microneedles are tiered.
15. The method of claim 1 , wherein the microneedles are hollow or porous.
16. The method of claim 15 , wherein the microneedles are hollow.
17. The method of claim 1 , wherein the microneedles have an average diameter of from 5 to 1,000 micrometers, an average length of from 5 to 1,500 micrometers, and an average distance from one another of from 5 to 1,000 micrometers.