Rational nanoparticle design: Optimization using insights from experiments and mathematical models

Abstract

Polymeric nanoparticles are highly tunable drug delivery systems that show promise in targeting therapeutics to specific sites within the body. Rational nanoparticle design can make use of mathematical models to organize and extend experimental data, allowing for optimization of nanoparticles for particular drug delivery applications. While rational nanoparticle design is attractive from the standpoint of improving therapy and reducing unnecessary experiments, it has yet to be fully realized. The difficulty lies in the complexity of nanoparticle structure and behavior, which is added to the complexity of the physiological mechanisms involved in nanoparticle distribution throughout the body. In this review, we discuss the most important aspects of rational design of polymeric nanoparticles. Ultimately, we conclude that many experimental datasets are required to fully model polymeric nanoparticle behavior at multiple scales. Further, we suggest ways to consider the limitations and uncertainty of experimental data in creating nanoparticle design optimization schema, which we call quantitative nanoparticle design frameworks.

Keywords: Multiscale mathematical modeling; Nanoparticle pharmacokinetics; Physiologically based pharmacokinetics; Polymeric nanoparticles; Rational nanoparticle design.