Glucose‐Responsive Microneedle Patch With Variable Crosslinking Density and Flexible Core–Shell Structure for Insulin Delivery

Abstract

Developing glucose-responsive microneedle patches with features of simple preparation, high insulin loading, and safety has a great contribution to the treatment of diabetic patients. In this work, a novel glucose-responsive core-shell microneedle patch is prepared from biocompatible materials by a facile process. The exterior glucose-responsive shell is composed of polyvinyl alcohol (PVA) and ɛ-polylysine modified with phenylboronic acid , and the inner flexible core is prepared by pure PVA loaded with insulin. The shell shows superior glucose-induced swelling and controlled insulin release ability due to the decomposition of borate ester bonds under the synergistic effect of glucose and water. The microneedle patch also features flexibility and high insulin loading capacity (36 IU cm −2 ). It shows high puncture efficiency (92%) and maintains a relatively complete morphology after being removed, enabling to reduce material residues in the skin. Moreover, the microneedle patch reveals a good hypoglycemic effect in diabetic rats, achieves a hypoglycemic rate similar to that of direct injection after swelling, and works effectively to prevent excess insulin transmission. The high glucose-responsive ability, simple preparation, high loading capacity, rapid hypoglycemic speed, high conformability to skin, and low component dissolution make this microneedle patch a suitable candidate for diabetic treatment.

Smart Responsive Microneedles for Controlled Drug Delivery

“…The pKa of PBA is 8.8-8.9 [38], which makes it prone to aggregation in the body, thereby limiting its ability to bind to glucose molecules to some extent [39]. To reduce the usage of glucose-responsive materials, microneedle patches with variable crosslinking densities in a core-shell structure [40], composite semi-interpenetrating hydrogel microneedles [41], and double-layered porous microneedle patches [42] have emerged. Additionally, modification of the structure of PBA can be employed to enhance its glucose sensitivity [43].…”

PVA-based bulk microneedles capable of high insulin loading and pH-triggered degradation for multi-responsive and sustained hypoglycemic therapy

“…It has been reported that hydrogen peroxide (H 2 O 2 ) produced by GOx during glucose oxidation can bind to phenylboronic acid esters, leading to further degradation of the phenylboronic acid ester structure, which increases the sensitivity of the glucose response and promotes rapid insulin release. 26–28 Therefore, phenyl borate and its derivatives (PBE) in combination with GOx have been extensively utilized for diabetes treatment. 29–31…”

Hollow-adjustable polymer microneedles for prolonged hypoglycemic effect on diabetic rats

“…Hence, it is essential to develop a MNs system that can effectively regulate BGLs for the maximum possible duration. Currently, two approaches have been adopted to achieve this goal, including responsive release and increasing drug loading while expanding drug release time [25][26] . A few studies have developed responsive release MNs patches, aiming to achieve a sustained and controlled drug release profile [27][28][29] .…”