Modelling Hollow Microneedle-Mediated Drug Delivery in Skin Considering Drug Binding

Area of Science:

• Pharmacology
• Biomedical Engineering
• Computational Biology

Background:

• Microneedle (MN)-based drug delivery offers an alternative to oral and hypodermic methods.
• An in silico model for hollow microneedle (HMN)-based drug delivery was developed.
• The model incorporates interstitial flow, drug binding kinetics, and absorption across skin, blood, and tissue compartments.

Purpose of the Study:

• To quantitatively understand HMN-based drug delivery using an in silico model.
• To investigate the influence of skin properties and HMN design on drug transport and absorption.
• To explore the impact of drug binding and interstitial flow on verapamil pharmacokinetics.

Main Methods:

• Developed an in silico model for HMN drug delivery.
• Utilized combined Marker and Cell and Immersed Boundary Methods to solve governing equations.
• Simulated verapamil transport in viscoelastic skin with specific, saturable binding.

Main Results:

• Viscoelastic skin impedes verapamil transport, reducing blood and tissue concentrations.
• Optimal MN length for skin concentration is not solely dependent on MN length.
• Decreasing tip diameter increases blood and bound tissue verapamil; increasing injection velocity increases free tissue verapamil.

Conclusions:

• Novelty lies in modeling verapamil metabolism in 2D viscoelastic skin with nonlinear binding.
• HMN tip diameter and injection velocity can regulate MN therapy efficacy.
• HMN design parameters are crucial for successful microneedle-mediated drug delivery.