Core-shell microneedle patch for h2o2 and ph cascade-triggered insulin delivery

Abstract

Disclosed are compositions and methods for microneedle patches comprising diblock copolymer micelles designed for pH cascade and H2O2 triggered insulin delivery.

1 - 9 . (canceled) 
     
     
         10 . A method of treating hyperglycemia in a subject comprising administering to the subject a microneedle patch comprising diblock copolymer micelles; wherein the diblock copolymer micelles comprise separately insulin and a glucose responsive enzyme; wherein the microneedles are coated with H 2 O 2  scavenging enzyme; and wherein the insulin dissociates from the micelle in an acidic and oxidative environment. 
     
     
         11 . The method of  claim 10 , wherein the hyperglycemia is a symptom of diabetes. 
     
     
         12 . A method of treating diabetes in a subject comprising administering to the subject a microneedle patch comprising diblock copolymer micelles; wherein the diblock copolymer micelles comprise separately insulin and glucose oxidase; wherein the microneedles are coated with H 2 O 2  scavenging enzyme; and wherein the insulin dissociates from the micelle in an acidic and oxidative environment. 
     
     
         13 . The method of  claim 10 , wherein the diblock copolymer comprises mPEG n -poly(2-(dimethylamino)ethyl methacrylate-4-(bromomethyl)phenylboronic acid) m   
       
         
           
           
               
               
           
         
         (MPEG n -P(DMAEMA-PBA) m ); wherein n can be between 1 and 8,000; and wherein m can be between 1 and 18,000. 
       
     
     
         14 . The method of  claim 13 , wherein the diblock copolymer micelles further comprise poly(vinyl alcohol) (PVA), wherein the PVA is incorporated into the micelle via acid-inert ester bonds between the phenylboronic acids of P(DMAEMA-PBA) and PVA. 
     
     
         15 . The method of  claim 13 , wherein the diblock copolymer micelles further comprise PVA methacrylate (m-PVA), wherein the PVA is incorporated into the micelle via acid-inert ester bonds between the phenylboronic acids of P(DMAEMA-PBA) and m-PVA 
     
     
         16 . The method of  claim 13 , wherein the glucose responsive enzyme is glucose oxidase. 
     
     
         17 . The method of  claim 13 , wherein the H 2 O 2  scavenging enzyme comprises catalase 
     
     
         18 . The method of  claim 13 , wherein the microneedles comprise a core and the diblock copolymer micelles are crosslinked to the microneedle core via non-cleavable covalent bond. 
     
     
         19 . The method of  claim 13 , wherein the H 2 O 2  scavenging enzyme comprises a peroxisome catalase nanogel.