Biological nanoparticles: Relevance as novel target drug delivery systems and leading chromatographic isolation approaches

Nanotechnology is one of the most promising technologies of the 21st century, and it is now presenting an enormous impact on target drug delivery. In this context, the recent use of natural vesicle-like nanoparticles such as extracellular vesicles (i.e., exosomes, microvesicles, and apoptotic bodies) and virus-like particles is rendering encouraging results mostly because these delivery systems present cargo versatility, favorable body circulating advantages, biocompatibility, immunogenicity, and the capacity to be modified superficially to increase their affinity to a certain target or to control their entrance to the cell. However, some of the biggest challenges toward their clinical implementation are poorly standardized processing operations due to their inherent heterogeneity and expensive, long-lasting, and difficult to scale isolation procedures that can also affect the stability of the particles. Under these circumstances, chromatographic procedures represent an attractive and favorable alternative to overcome their downstream processing. Moreover, even when standardized chromatographic purification protocols are still in development, great achievements have been made using size exclusion, ionic exchange, hydrophobic interaction, and affinity protocols, mostly because of the correct harnessing of the nanovesicle membrane properties. In this sense, this review focuses on presenting the current understanding on the most promising therapeutic biological nanoparticles and the chromatographic isolation approaches employed in their recovery, providing at the same time recent findings and a general overview of the aspects that might impact the outcome of chromatographic techniques for this application.