Microneedles Integrated with ZnO Quantum-Dot-Capped Mesoporous Bioactive Glasses for Glucose-Mediated Insulin Delivery

Abstract

A self-responsive insulin delivery system is highly desirable because of its high sensitivity dependent on blood glucose levels. Herein, a smart pH-triggered and glucose-mediated transdermal delivery system, insulin-loaded and ZnO quantum dots (ZnO QDs) capped mesoporous bioactive glasses (MBGs) integrated with microneedles (MNs), was developed to achieve control and painless administration. ZnO QDs as a promise pH-responsive switch were employed to cap the nanopores of MBGs via electrostatic interaction. The drug (insulin) and glucose-responsive factor (glucose oxidase/catalase, GO x /CAT) were sealed into the pores of MBGs. GO x /CAT in the MBGs could catalyze glucose to form gluconic acid, resulting decrease in the local pH. The ZnO QDs on the surface of the MBGs could be dissolved in the acidic condition, leading to disassembly of the pH-sensitive MBGs and then release of preloaded insulin from the MBGs. As a result of administration in a diabetic model, an excellent hypoglycemic effect and lower hypoglycemia risk were obtained. These results indicate that as-prepared pH-triggered and glucose-mediated transdermal delivery systems have hopeful applications in the treatment of diabetes.

Advances in transdermal insulin delivery

“…Upon exposure to H 2 O 2 , the phenylboronic ester on the surface of the MSNs was oxidized, resulting in the destruction of the host-guest complexation and subsequent release of the preloaded insulin. Recently, mesoporous bioactive glasses was employed as the insulin carrier and integrated with MN device for glucose-responsive insulin delivery [241]. In this design, the porous bioactive glasses loaded with insulin and two enzymes (GOx/CAT) were capped with pH-sensitive ZnO quantum dots as "gatekeepers".…”

Progress in Microneedle-Mediated Protein Delivery

“…Since ZnO QDs are dissolvable at a low pH, they can act as pH-sensitive agents (Figure 7). In vivo studies showed the achievement of prolonged moderate blood glucose control by the glucose-responsive MNs, while BGLs dropped quickly when subcutaneous injections were used [134]. Figure 6.…”

“…Amplified glucose levels can effectively diffuse and activate the release of β-cells on the tips of MNs. The amplified signal showed significant effective glucose control for almost 8 h compared with other treatments lacking the live/synthetic part or even with one of the enzymes involved [134]. Bioactive glass nanoparticles (BGN) can be manufactured by BGN soles through gelation under high temperatures.…”

“…The catalase (CAT) enzyme is responsible for reducing the harm caused by H 2 O 2 on the surrounding tissue. Reprinted with permission from [134].…”

“…Higher amounts of glucose diffuse and make the living part of the system secrete insulin effectively. Reprinted with permission from [134].…”