Intra-nanoparticle Drug-protein Interactions Mediate Sequential Therapeutic Release

Controlled drug delivery systems have important implications in many therapeutic applications to improve patient health, but it remains challenging to deliver therapeutics to specific target sites while being released at controlled rates to minimize the off-target accumulation. Here, we report a drug (e.g., vancomycin)–modulating other drug release strategies in human serum albumin (HSA)-based nanoparticles (NPs) to achieve multiple drug encapsulation and controlled release of drugs. Without external stimuli but only with water, the release kinetics of drugs such as sulfasalazine and epidermal growth factor can be modulated by adding vancomycin. The mechanistic study suggests that the release kinetics are related to the secondary structure of albumin through the interactions between drugs and HSA. Our strategy achieved controlled drug delivery through modulating the secondary structure of albumin with a water-soluble drug as a modulator, which provides a promising way to simultaneously deliver multiple drugs while releasing in a predicted and sustained manner.