Stability and Diffusion Properties of Insulin in Dissolvable Microneedles: A Multiscale Simulation Study

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Computational Chemistry

Background:

• Microneedle (MN) technology offers an efficient and safe method for insulin delivery for diabetes management.
• Further research is needed to confirm insulin activity and understand release mechanisms in MNs for clinical use.

Purpose of the Study:

• To investigate insulin's structural stability and diffusion in polyvinyl alcohol (PVA) and hyaluronic acid (HA) solutions using molecular dynamics simulations.
• To elucidate the interaction between insulin and polymer matrices to inform the design of insulin-loaded dissolvable MNs.

Main Methods:

• Employed all-atom molecular dynamics (MD) and coarse-grained dissipative particle dynamics (DPD) simulations.
• Analyzed insulin's structural stability, interaction modes with PVA and HA, and diffusion coefficients.

Main Results:

• Polymer presence did not cause irreversible changes to insulin's secondary structure, ensuring in vivo activity.
• Insulin diffusion coefficient was higher in HA than in PVA solutions.
• Identified distinct diffusion mechanisms: Brownian motion in HA/water and hopping in PVA due to intermolecular interactions.

Conclusions:

• The study provides crucial insights into insulin behavior within polymer matrices relevant to dissolvable MN development.
• Findings offer theoretical guidance for optimizing the formulation of insulin-loaded microneedles for diabetes therapy.