Cross-Linking-Density-Changeable Microneedle Patch Prepared from a Glucose-Responsive Hydrogel for Insulin Delivery

Abstract

To simplify the preparation process of a glucose-responsive microneedle patch, a cross-linking-density changeable microneedle patch was designed. The microneedle patch was made up of a hydrogel formed by phenylboronic acid-grafted polyallylamine and poly­(vinyl alcohol) (PVA). The gel was cross-linked by boronate ester bonds between phenylboronic acid groups and PVA. It still had fluidity and could be filled into a mold to prepare microneedle patches. Moreover, insulin could be directly loaded into the microneedle patch by mixing with the gel. The boronate ester bond would be broken in the presence of glucose, resulting in a decrease in the cross-linking density. Therefore, the gel could achieve a greater swelling degree and insulin could be released faster. In addition, PVA chains were crystallized by repeatedly freezing and thawing to improve the mechanical strength of the microneedle patch. In terms of glucose-dependent insulin release, the gel showed good glucose-responsive insulin-release ability. Through additional ion cross-linking, the microneedle patch could also control the insulin release according to glucose concentration. In the hypoglycemic experiment of diabetic rats, the microneedle patch effectively pierced the skin and slowly released insulin.

Stimuli-Responsive Microneedles as a Transdermal Drug Delivery System: A Demand-Supply Strategy

“…Currently, many “closed-loop” glucose-responsive MN systems that work on various principles are available. For instance: (i) electronic glucose-monitoring sensor-based MNs that delivers insulin by sensing elevated BGL; , (ii) glucose oxidase (GOx) enzyme-based glucose-responsive MNs that triggers the release of encapsulated insulin in response to the GOx-catalyzed environmental changes such as acidic pH or hypoxia; and (iii) phenylboronic acid (PBA) chemical-based glucose-responsive MNs that undergo reversible swelling in response to hyperglycemia, which further facilitates a diffusion control of the encapsulated insulin. , …”

“…This could hinder the ability of MNs to deliver insulin in an on-demand fashion for a longer period. Although the dissociated nanoparticles/nanovesicles are biocompatible, they could face issues in terms of biodegradability . Therefore, an ideal glucose-responsive MN system should directly release the insulin from the MN matrix for a longer period without leaving any polymeric debris in the body.…”

Recent Advances in Polymer Microneedles for Drug Transdermal Delivery: Design Strategies and Applications

“…[ 177 ] Besides high incidence rate, diabetes can cause many serious complications, such as renal failure, lower limb amputation, and retinopathy. [ 178 ] Therefore, how to treat diabetes effectively has attracted great attention. Insulin is the only hormone in the body that can lower blood glucose.…”

“…Thus, in the case of hyperglycemia, microneedle patch swells and releases insulin rapidly. [ 178,192 ] Chen et al. [ 178 ] designed a crosslinking density variable microneedle patch, which is composed of a hydrogel formed by PVA and PBA‐grafted polyallylamine.…”

“…Thus, in the case of hyperglycemia, microneedle patch swells and releases insulin rapidly. [178,192] Chen et al [178] designed a crosslinking density variable microneedle patch, which is composed of a hydrogel formed by PVA and PBA-grafted polyallylamine. The microneedle patch can effectively penetrate the skin and control the release of insulin according to the glucose concentration.…”