Influence of Structural Features on the Cellular Uptake Behavior of Non-Targeted Polyester-Based Nanocarriers

The development of delivery systems efficiently uptaken by cells is of due importance since sites of drug action are generally localized in subcellular compartments. Herein, naked and core-shell polymeric nanoparticles (NPs) have been produced from poly(lactic-co-glycolic acid)-PLGA, poly(ethylene oxide)-b-poly(e-caprolactone)-PEO-b-PCL, and poly(ethylene oxide)-b-poly(lactic acid)-PEO-b-PLA. The nanostructures are characterized and the cellular uptake behavior is evaluated. The data evidence that cellular uptake is enhanced as the length of the hydrophilic PEO-stabilizing shell reduces and that high negative surface charge restricts cellular uptake. Furthermore, NPs of higher degree of hydrophobicity (PEO-b-PCL) are more efficiently internalized as compared to PEO-b-PLA NPs. Accordingly, taking into account our recent published results([1]) and the findings of the current investigation, there should be a compromise regarding protein fouling and cellular uptake as resistance to nonspecific protein adsorption and enhanced cellular uptake are respectively directly and inversely related to the length of the PEO-stabilizing shell.