Characterization of micromechanical properties of nanocomposite gel microparticles for lung therapy

Abstract

Lung cancer is the leading cause of cancer-related deaths in the US, and non-small cell lung cancer makes up 85% of cases. One promising targeted drug delivery strategy is the venous filtration system, in which IV injection is used to deliver gel microparticles (GMPs) loaded with drug nanoparticles to lung capillaries. Size and modulus must be controlled to optimize accumulation and clearance of the GMPs in the lungs, and here we focus on factors that affect the modulus. We measure modulus in one of two ways, osmotic compression using dextran solution to find the bulk modulus, and AFM indentation with a silica probe to find the Young’s modulus. We vary parameters including GMP size, type of oil used in GMP formulation, and nanoparticle concentration and find that there is no effect on modulus using osmotic compression, but find conflicting results with respect to nanoparticle concentration using AFM indentation. We also find that the GMPs degrade quickly in vitro at 37\(^{o}\)C within a week, agreeing with our in vivo results, and the modulus decreases rapidly as well. However, if frozen the GMPs can be frozen for long lengths of time without affecting modulus. Finally, we simulate AFM indentation using COMSOL Multiphysics 4.3b in order to validate the method and find good agreement with experimental data when using Hertz contact theory and assuming incompressibility.