Physiologically Relevant Mechanics of Biodegradable Polyester Nanoparticles

Despite the extensive use of biodegradable polyester nanoparticles for drug delivery, and reports of the strong influence of nanoparticle mechanics on nano-bio interactions, there is a lack of systematic studies on the mechanics of these nanoparticles under physiologically relevant conditions. Here, we report indentation experiments on poly(lactic acid) and poly(lactide-co-glycolide) nanoparticles using atomic force microscopy. While dried nanoparticles were found to be rigid at room temperature, their elastic modulus was found to decrease by as much as 30 fold under simulated physiological conditions (i.e., in water at 37 °C). Differential scanning calorimetry confirms that this softening can be attributed to the glass transition of the nanoparticles. Using a combination of mechanical and thermoanalytical characterization, the plasticizing effects of miniaturization, molecular weight, and immersion in water were investigated. Collectively, these experiments provide insight for experimentalists exploring the relationship between polymer nanoparticle mechanics and in vivo behavior.