Optimal loading of hydrogel-based drug-delivery systems

TL;DR

This paper develops a mathematical model and optimization method to design hydrogel drug-delivery systems with controlled release profiles, minimizing burst effects and tuning release rates through initial drug distribution and gel stiffness.

Contribution

It introduces a novel optimization approach for initial drug placement in hydrogels, accounting for nonlinear elasticity and swelling, to achieve desired release profiles.

Findings

Optimal initial drug distribution involves a core and boundary packets.

Stiffer hydrogels reduce swelling but can accelerate drug release.

The method effectively mitigates burst release effects.

Abstract

Drug-loaded hydrogels provide a means to deliver pharmaceutical agents to specific sites within the body at a controlled rate. The aim of this paper is to understand how controlled drug release can be achieved by tuning the initial distribution of drug molecules in a hydrogel. A mathematical model is presented for a spherical drug-loaded hydrogel. The model captures the nonlinear elasticity of the polymer network and thermodynamics of swelling. By assuming that the drug molecules are dilute, the equations for hydrogel swelling and drug transport partially decouple. A fast optimisation method is developed to accurately compute the optimal initial drug concentration by minimising the error between the numerical drug-release profile and a target profile. By taking the target drug efflux to be piecewise constant, the optimal initial configuration consists of a central drug-loaded core with isolated drug packets near the free boundary of the hydrogel. The optimal initial drug concentration is highly effective at mitigating the burst effect, where a large amount of drug is rapidly released into the environment. The hydrogel stiffness can be used to further tune the rate of drug release. Although stiffer gels lead to less swelling and hence reduce the drug diffusivity, the drug-release kinetics are faster than for soft gels due to the decreased distance that drug molecules must travel to reach the free surface.