Electrostatic-Interaction-Aided Microneedle Patch for Enhanced Glucose-Responsive Insulin Delivery and Three-Meal-Per-Day Blood-Glucose Regulation

Abstract

The phenylborate-ester-cross-linked hydrogel microneedle patch (MNP) was promising in the diabetic field for the glucose-responsive insulindelivering property and simple fabrication process. However, the unfit design of the charging microneedle network limited the improvement of blood-glucose regulating performances. In this work, insulin-loaded phenylborate-ester-crosslinked MNPs, with the polyzwitterion property, were constructed based on the modified ε-polylysine and poly(vinyl alcohol). The relationship between the charging nature of the MNP network and insulin release was verified by regulating the content of postprotonated positively charged amino groups. The elaborately designed MNP possessed improved glucose-responsive insulindelivering performance. The in vivo study revealed the satisfactory results on blood-glucose regulation by the optimized MNP under the mimic three-mealper-day mode. Moreover, the insulin bioactivity in the MNP could be maintained for 2 weeks under 25 °C. In summary, this work developed an effective strategy to improve the glucose-responsive phenylborateester-cross-linked MNP and enhance its potential for clinical transformation.

Designing Polyelectrolyte Microneedles Based on Borylated Poly(β-aminoester) Polymers To Enhance Transdermal pH-Controlled Delivery of Nucleic Acids

“…It is important to consider that the stability of the boronic acids/sugar adducts is usually directly related to the p K a of the boronic acid itself and the pH of the medium in which the interaction is occurring. A couple of recent studies − have illustrated the potential of this fluorinated phenyl boronic acid fragment in glucose-responsive insulin transdermal delivery systems. In the context of gene delivery, these types of borylated units have been nicely studied by Professor Kataoka’s group; ,, however, to the best of our knowledge, they have never been applied to a microneedle-based transdermal system.…”