Two-layered dissolving microneedles formulated with intermediate-acting insulin.

Area of Science:

• Pharmaceutical Sciences
• Biomaterials Engineering
• Endocrinology

Background:

• Diabetes management often relies on frequent subcutaneous insulin injections.
• Developing alternative, patient-friendly insulin delivery systems is crucial for improving adherence and outcomes.
• Intermediate-acting insulin formulations, like protamine sulfate insulin (PSI), require effective delivery methods for sustained therapeutic action.

Purpose of the Study:

• To prepare and characterize two-layered dissolving microneedles (DMs) loaded with protamine sulfate insulin (PSI).
• To evaluate the pharmacodynamic performance and hypoglycemic effects of PSI-loaded DMs in a rat model.
• To assess the stability and in vitro release characteristics of PSI from the DMs.

Main Methods:

• Fabrication of two-layered dissolving microneedles with specific dimensions and PSI loading.
• In vitro stability assessment of PSI within DMs at varying temperatures (4 °C and 40 °C).
• In vivo pharmacodynamic study in rats to compare hypoglycemic effects of DMs versus subcutaneous injections, measuring plasma glucose levels over time.

Main Results:

• The prepared DMs had a length of approximately 497 μm and contained 0.51 IU of PSI.
• High PSI recovery (99.9%) was observed after three months at 4 °C, with slightly lower recovery (97.5%) at 40 °C.
• In vivo studies demonstrated comparable prolonged hypoglycemic effects and relative pharmacologic availability (91.4–100.2%) between PSI DMs and traditional subcutaneous injections.

Conclusions:

• Two-layered dissolving microneedles are a viable and effective delivery system for protamine sulfate insulin.
• PSI-loaded DMs provide prolonged hypoglycemic effects comparable to subcutaneous injections in rats.
• These DMs represent a promising alternative to conventional insulin injections, potentially improving patient compliance and therapeutic convenience.