Exendin-4–encapsulated dissolving microneedle arrays for efficient treatment of type 2 diabetes

Abstract

Dissolving microneedles (DMNs) are microscopic needles capable of delivering encapsulated compounds and releasing them into the skin in a minimally invasive manner. Most studies indicate that encapsulating therapeutics in DMNs is an efficacious approach; however, the importance of evaluating the activity of encapsulated compounds, during the fabrication process, has not been examined in detail. Conducting an analysis of thermal, chemical, and physical stress factors, including temperature, pH, and the interaction of the polymer and therapeutics mixture during preparation, is essential for retaining the activity of encapsulated therapeutics during and after fabrication. Here, we optimised the thermal, chemical, and physical parameters for the fabrication of exendin-4 (Ex-4)-encapsulated DMNs (Ex-4 DMNs). Ex-4, a peptide agonist of glucagon-like peptide (GLP) receptor, is used for glycaemic control in patients with type 2 diabetes. Our findings indicate that optimising the parameters involved in DMN fabrication retained the activity of Ex-4 by up to 98.3 ± 1.5%. Ex-4 DMNs reduced the bloodglucose level in diabetic mice with efficiency similar to that of a subcutaneous injection. We believe that this study paves way for the commercialisation of an efficient and minimally invasive treatment for patients with type 2 diabetes.

3D printed microneedle patches using stereolithography (SLA) for intradermal insulin delivery

“…Although the plasma glucose level versus time profile was similar to previous findings [53][54][55][56][57] the steady state plasma glucose level was maintained up to 4 h while the untreated group (negative control) remained unchanged (no hypoglycaemia) for the same period. These findings suggest that insulin is being released from the 3D printed MNs to the mice blood stream via passive diffusion to blood capillary.…”

Recent advances in microneedles-mediated transdermal delivery of protein and peptide drugs

“…Another potential approach to combat diabetes is using glucagon-like peptide-1 receptor agonists 173 , 176 , 177 . Chen et al.…”

Microneedle Arrays Combined with Nanomedicine Approaches for Transdermal Delivery of Therapeutics

“…Concerning this issue, MN technology could be an interesting delivery system capable of smoothly passing SC and delivering proteins into the systemic circulation [ 150 ]. MN technology has been widely applied in recent years for the effective delivery of proteins, including antigen [ 151 ], antibody [ 152 ], insulin [ 153 ], exendin-4 [ 154 ], and lysozyme [ 155 ]. For example, introducing MN technology to insulin delivery has been used as a non-invasive, painless, and easy-to-handle administration technique in tuning the glucose level in diabetic patients.…”