Physicochemical Interactions of Nano carriers in Plasma: Possible Impacts on Their Cell Uptake

Nanoparticle-based drug delivery systems offer tremendous potential for the precise and targeted delivery of drugs, proteins, and genetic materials, even to subcellular locations within organisms. Despite extensive research into the cellular uptake of nanocarriers with diverse sizes and shapes, there remains a critical gap in understanding their interactions and stability within colloidal suspensions in plasma, particularly regarding the efficiency of cell uptake and the mechanisms that govern it. The surface properties of nanocarriers are pivotal in dictating their dispersion and aggregation behaviors, which are influenced by complex physicochemical interactions—such as electrostatic, van der Waals, and hydrophobic forces—between the nanoparticles and the biomolecular components in body fluids, including proteins and ions. These interactions can significantly modulate cell uptake, either enhancing or impeding the process, potentially inducing toxicity or compromising therapeutic efficacy. Under certain conditions, the disintegration of nanocarriers may lead to drug-nanocarrier separation, facilitating direct drug transfer to the cell membrane. This review delves into the intricate colloidal dynamics of nanocarriers as they traverse physiological environments prior to cellular uptake. By exploring the key physicochemical interactions and underlying sub-processes, we offer a comprehensive framework for evaluating drug delivery systems from a pharmaceutical standpoint. Additionally, the review outlines strategies to manipulate nanocarrier design and behavior, enabling enhanced control over their uptake mechanisms and ultimately improving the efficiency and safety of drug delivery.