Microarray for delivery of therapeutic agent, methods of use, and methods of making
Devices and methods for using and manufacturing microstructure arrays are described.
1. A method of making an array of microstructures comprising:
(a) dissolving or suspending at least one therapeutic agent and at least one polymer in one or more solvents to form a polymer matrix solution or suspension;
(b) dispensing the polymer matrix solution or suspension on a mold having an array of microstructure cavities;
(c) filling the microstructure cavities in the mold with the polymer matrix solution or suspension;
(d) removing excess polymer matrix solution or suspension on the mold surface;
(e) a first drying step comprising drying the polymer matrix solution or suspension at a temperature of about 5-50° C. in a chamber having a partial pressure of water of about 0.01 mTorr to about 203 Torr or a relative humidity of about 50-95% for about 5-30 minutes;
(f) a second drying step comprising drying the polymer matrix solution or suspension at about 5-50° C. for about 30 minutes in an oven without controlled partial pressure of water or relative humidity to form an array of microstructures; and
(g) drying the microstructures under vacuum at about 5-50° C.
2. The method of claim 1 , wherein step (a) comprises:
(i) dissolving or suspending the at least one therapeutic agent in a first solvent to form a therapeutic agent solution or suspension;
(ii) dissolving the at least one polymer in a second solvent to form a polymer solution or suspension; and
(iii) mixing the therapeutic agent solution or suspension and the polymer solution or suspension to form the polymer matrix solution or suspension.
3. The method of claim 1 , wherein the chamber uses convection, conduction, or radiation for drying.
4. The method of any previous claim, further comprising:
dispensing a basement or backing layer on the mold surface; and
drying the basement or backing layer.
5. The method of claim 4 , wherein drying the basement or backing layer comprises drying in an oven at about 5-50° C.
6. The method of claim 4 , wherein drying the basement or backing layer comprises drying in a compressed dry air box with controlled air flow prior to drying in an oven.
7. The method of any one of claim 4 , further comprising:
affixing the basement or backing layer to a substrate.
8. The method of claim 7 , wherein the substrate is selected from a pressure sensitive adhesive and a UV cured adhesive.
9. The method of claim 7 , further comprising:
affixing the basement or backing layer to the substrate using a nonwoven or porous film double coated with adhesive.
10. The method of claim 1 , further comprising:
demolding the microstructure array.
11. The method of claim 4 , further comprising demolding the microstructure array after drying the basement or backing layer.
12. The method of claim 1 , further comprising:
applying a wetting agent to the mold prior to step (b).
13. The method of claim 12 , wherein the wetting agent is selected from calcium carbonate, ethyl acetate, a silicone fluid, oxygen plasma, or a silicone polyether surfactant.
14. The method of claim 1 , wherein step (c) comprises pressurization of at least about 10 psi above atmospheric.
15. The method of claim 1 , wherein step (c) uses soluble gases.
16. The method of claim 15 , wherein the soluble gas is selected from CO 2 and CH 4 .
17. The method of claim 1 , wherein step (a) further comprises dissolving at least one of a sugar, a surfactant, or an antioxidant in the one or more solvents.
18. The method of claim 1 , further comprising dissolving a sugar in the polymer matrix solution or suspension after step (a).
19. The method of claim 17 , wherein the sugar is selected from sorbitol, sucrose, trehalose, fructose, or dextrose.
20. The method of claim 17 , wherein the surfactant is selected from Polysorbate 20 or Polysorbate 80.
21. The method of claim 17 , wherein the antioxidant is selected from methionine, cysteine, D-alpha tocopherol acetate, EDTA, or vitamin E.
22. The method of claim 1 , wherein step (a) comprises dissolving about 10-40% by weight of the at least one polymer in the one or more solvents.
23. The method of claim 1 , wherein the at least one therapeutic agent is selected from a drug, a small molecule, a peptide or protein, or a vaccine.
24. The method of claim 1 , wherein the suspension is a liquid in liquid suspension or a solid in liquid suspension.
25. The method of claim 2 , wherein at least one of the first or second solvents is water.