A Pioneering Review on Quantitative Analysis of the Effect of Macromolecular Crowding on Drug Transport and Release: Current Implications

Abstract

The intricate interplay of macromolecules within biological systems significantly influences the behavior of therapeutic agents, making the understanding of macromolecular crowding crucial for the advancement of drug delivery technologies. This review article provides a comprehensive analysis of the effects of macromolecular crowding on drug transport and release, emphasizing its quantitative impact and current implications in the field. Macromolecular crowding, characterized by the dense packing of proteins, nucleic acids, and other polymers in cellular environments, alters key biophysical properties, such as viscosity, diffusion rates, and molecular interactions. These changes critically affect the pharmacokinetics and pharmacodynamics of drugs, presenting both challenges and opportunities for therapeutic design and application. The article delves into the theoretical foundations of macromolecular crowding, grounded in thermodynamics and statistical mechanics, to elucidate how such conditions modulate drug behavior. Through an integrated review of empirical research and advanced simulation models, it highlights innovative strategies to harness crowding effects for optimizing drug delivery systems. The discussion extends to the evaluation of experimental methodologies and measurement techniques, including spectroscopy and imaging that are pivotal in quantifying the implications of crowding. This pioneering review not only synthesizes current research but also identifies gaps in knowledge and proposes directions for future investigation. It aims to serve as a vital resource for researchers and practitioners, fostering the development of more effective drug delivery mechanisms by leveraging the nuanced understanding of macromolecular crowding. This work underscores the potential of this underexplored area to significantly influence the next generation of pharmaceutical formulations and therapeutic interventions.

Keywords:

• Macromolecular crowding
• drug transport
• drug release dynamics
• cellular pharmacokinetics
• biophysical environment
• drug delivery systems
• therapeutic efficacy

Disclosure statement

No potential conflict of interest was reported by the author(s).