The in vivo fate of polymeric micelles.

This review aims to provide a systemic analysis of the in vivo, as well as subcellular, fate of polymeric micelles (PMs), starting from the entry of PMs into the body. Few PMs are able to cross the biological barriers intact and reach the circulation. In the blood, PMs demonstrate fairly good stability mainly owing to formation of protein corona despite controversial results reported by different groups. Although the exterior hydrophilic shells render PMs "long-circulating", the biodistribution of PMs into the mononuclear phagocyte systems (MPS) is dominant as compared with non-MPS organs and tissues. Evidence emerges to support that the copolymer poly(ethylene glycol)-poly(lactic acid) (PEG-PLA) is first broken down into pieces of PEG and PLA and then remnants to be eliminated from the body finally. At the cellular level, PMs tend to be internalized via endocytosis due to their particulate nature and disassembled and degraded within the cell. Recent findings on the effect of particle size, surface characteristics and shape are also reviewed. It is envisaged that unraveling the in vivo and subcellular fate sheds light on the performing mechanisms and gears up the clinical translation of PMs.