Converting short-acting insulin into thermo-stable longer-acting insulin using multi-layer detachable microneedles.

The detachable dissolving microneedles (DDMNs) feature an array of needles capable of being separated from the base sheet during administration. Here they were fabricated to address delivery efficiency and storage stability of insulin. The constructed insulin-DDMN is multi-layered, with 1) a hard tip cover layer; 2) a layer of regular short-acting insulin (RI) mixed with hyaluronic acid (HA) and sorbitol (Sor) which occupies the taper tip region of the needles; 3) a barrier layer situated above the RI layer; and 4) a fast-dissolving layer connecting the barrier layer to the base sheet. RI entrapped in DDMNs exhibited enhanced thermal stability; it could be stored at 40°C for 35 days without losing significant biological activity. Differential scanning calorimetric analysis revealed that the HA-Sor matrix could improve the denaturation temperature of the RI from lower than room temperature to 186°C. Tests in ex vivo porcine skin demonstrated RI delivery efficiency of 91±1.59%. Experiments with diabetic rats revealed sustained release of RI, i.e., when compared to subcutaneous injection with the same RI dose, RI-DDMNs produced slower absorption of insulin into blood circulation, delayed onset of hypoglycemic effect, longer serum insulin half-life, and longer hypoglycemic duration.

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Copyright © 2024. Published by Elsevier Inc.

Déclaration de conflit d'intérêts

Declaration of interest This work was funded by Center of Excellence in Materials and Bio-Interfaces at Chulalongkorn University and Mineed Technology Company. T.P. was financially supported by the Second Century Fund (C2F) from Chulalongkorn University. Mineed Technology Company owns the detachable microneedle patent.