Methods and compositions related to physiologically responsive microneedle delivery systems

1. A method of treating a disease in a subject in need thereof, the method comprising:

a) providing a microneedle patch to the subject, wherein the microneedle patch comprises:

i) a plurality of microneedles each having a base end and a tip;

ii) a substrate to which the base ends of the microneedles are attached or integrated;

iii) at least one reservoir which is in connection with the base ends of the microneedles array, wherein the reservoir comprises an agent delivery system, wherein the agent delivery system comprises an agent to be transported across the biological barrier, or a means for producing an agent to be transported across the biological barrier, and a means for detecting a physiological signal from the recipient wherein said means for producing an agent to be transported across the biological barrier and said means for detecting a physiological signal both comprise cells; and

iv) a signal amplifier system integrated within the microneedles, wherein the signal amplifier system comprises a component capable of amplifying the physiological signal from the recipient, wherein the means for producing an agent to be transported across the biological barrier produces an agent, or changes the amount of agent produced, based on an amplified signal from the signal amplifier system;

b) inserting the microneedles into the biological barrier; and

c) delivering the agent through the microneedles and into the biological barrier, wherein the amount or volume of agent delivered is determined by a signal received from the signal amplifier system.

2. The method of claim 1 , wherein the cells are pancreatic β cells or stem cell-differentiated human pancreatic cells.

3. The method of claim 1 , wherein the reservoir is composed of a material matrix that can be used to deliver cell products.

4. The method of claim 3 , wherein the reservoir comprises an alginate microgel.

5. The method of claim 1 , wherein the reservoir comprises a therapeutic, prophylactic, or diagnostic agent.

6. The method of claim 1 wherein the agent is selected from the group consisting of peptides, proteins, carbohydrates, nucleic acid molecules, lipids, organic molecules, biologically active inorganic molecules, and combinations thereof.

7. The method of claim 6 , wherein the agent is insulin.

8. The method of claim 1 , wherein the signal amplifier system magnifies a signal, thereby altering the volume or amount of agent to be transported based on the strength of the signal present in the subject.

9. The method of claim 8 , wherein the physiological signal is a biological substance in the subject.

10. The method of claim 1 , wherein the agent delivery system comprises a feedback component, such that volume or amount of the agent to be transported across the biological barrier can be altered based on the physiological signal.

11. The method of claim 10 , wherein the physiological signal from the recipient is insufficient to be detected by the feedback component without amplification from the signal amplifier system.

12. The method of claim 11 , wherein the physiological response in the subject comprises physiological environment factors, including pH, temperature, blood glucose levels and other biomarkers.

13. The method of claim 12 , wherein the signal is glucose.

14. The method of claim 1 , wherein the signal amplifier system comprises self-assembled polymeric nanosized vesicles.

15. The method of claim 14 , wherein the glucose signal amplifier comprises glucose oxidase, α-amylase, and glucoamylase.

16. The method of claim 1 , wherein the signal amplifier system is in the tip of the microneedle.

17. The method of claim 1 , wherein the subject has been diagnosed with diabetes.