Brownian dynamics simulation of insulin microsphere formation from break-up of a fractal network

J Chem Phys. 2011 Jan 14;134(2):024902. doi: 10.1063/1.3517865.

Abstract

Motivated by a recent experiment on insulin microsphere formation where polyethylene glycol (PEG) is used as the precipitating agent, we have developed a simple theoretical model that can predict the formation of a fractal network of insulin monomers and the subsequent break-up of the fractal network into microsphere aggregates. In our approach the effect of PEG on insulin is modeled via a standard depletion attraction mechanism via the Asakura-Oosawa model. We show that even in the context of this simple model, it is possible to mimic important aspects of the insulin experiment in a brownian dynamics simulation. We simulate the effect of changing temperature in our model by changing the well depth of the Asakura-Oosawa potential. A fractal network is observed in a "deep quench" of the system, followed by a "heating" that results in a break-up of the network and subsequent formation of microspheres.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Insulin / chemistry*
  • Kinetics
  • Molecular Dynamics Simulation*
  • Polyethylene Glycols / chemistry*

Substances

  • Insulin
  • Polyethylene Glycols