Mathematical model accurately predicts protein release from an affinity-based delivery system

J Control Release. 2015 Jan 10;197:69-77. doi: 10.1016/j.jconrel.2014.10.032. Epub 2014 Nov 6.

Abstract

Affinity-based controlled release modulates the delivery of protein or small molecule therapeutics through transient dissociation/association. To understand which parameters can be used to tune release, we used a mathematical model based on simple binding kinetics. A comprehensive asymptotic analysis revealed three characteristic regimes for therapeutic release from affinity-based systems. These regimes can be controlled by diffusion or unbinding kinetics, and can exhibit release over either a single stage or two stages. This analysis fundamentally changes the way we think of controlling release from affinity-based systems and thereby explains some of the discrepancies in the literature on which parameters influence affinity-based release. The rate of protein release from affinity-based systems is determined by the balance of diffusion of the therapeutic agent through the hydrogel and the dissociation kinetics of the affinity pair. Equations for tuning protein release rate by altering the strength (KD) of the affinity interaction, the concentration of binding ligand in the system, the rate of dissociation (koff) of the complex, and the hydrogel size and geometry, are provided. We validated our model by collapsing the model simulations and the experimental data from a recently described affinity release system, to a single master curve. Importantly, this mathematical analysis can be applied to any single species affinity-based system to determine the parameters required for a desired release profile.

Keywords: Affinity release; Controlled release; Dimensionless analysis; Mathematical modeling; Protein release; Protein stability.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chondroitin ABC Lyase / chemistry*
  • Diffusion
  • Drug Delivery Systems*
  • Fibroblast Growth Factor 2 / chemistry*
  • Hydrogels
  • Kinetics
  • Models, Theoretical*
  • Recombinant Fusion Proteins / chemistry*
  • src Homology Domains

Substances

  • Hydrogels
  • Recombinant Fusion Proteins
  • Fibroblast Growth Factor 2
  • Chondroitin ABC Lyase