Enhanced cancer immunotherapy by microneedle patch-assisted delivery
Disclosed herein are self-degradable microneedle devices for the controlled-release of an immunotherapeutic agent. Also disclosed are methods for treating a disease (for example, cancer) using a self-degradable microneedle patch for the sustained delivery of an immunotherapeutic agent (for example, a PD1 antibody).
1. A method for treating a skin cancer in a subject in need thereof, comprising:
providing a microneedle patch to a subject, wherein the microneedle patch comprises:
a plurality of microneedles each having a base end and a tip;
a substrate to which the base ends of the microneedles are attached or integrated;
acid-degradable nanoparticles, wherein the nanoparticles encapsulate an immunotherapeutic agent and a pH altering agent;
inserting the microneedles into a biological barrier, wherein the pH altering agent decreases the pH within the acid-degradable nanoparticles, and wherein the decrease in the pH degrades the nanoparticle and releases the immunotherapeutic agent into the subject in a controlled-release manner;
wherein the immunotherapeutic agent comprises an anti-PD1 antibody and an anti-CTLA4 antibody.
2. The method of claim 1 , wherein the skin cancer is melanoma.
3. The method of claim 1 , wherein the pH altering agent is glucose oxidase.
4. The method of claim 1 , wherein the acid-degradable nanoparticles comprise modified dextran.
5. The method of claim 1 , wherein the microneedles comprise hyaluronic acid.
6. The method of claim 1 , wherein the anti-PD1 antibody is nivolumab.
7. The method of claim 1 , wherein the anti-PD1 antibody is pembrolizumab.
8. The method of claim 1 , wherein the anti-CTLA4 antibody is ipilimumab.
9. The method of claim 1 , wherein the acid-degradable nanoparticles further comprise a surfactant.
10. The method of claim 9 , wherein the surfactant is alginate.