Amphiphilic poly(amino acid) based micelles applied to drug delivery: the in vitro and in vivo challenges and the corresponding potential strategies.

Core-shell structured micelles produced from an amphiphilic block copolymer are promising drug delivery vehicles because their hydrophobic core can encapsulate hydrophobic drugs through hydrophobic interactions and their hydrophilic shell can prolong their circulation in the blood. However, the low cargo capacity and the lack of stability in the blood are major problems associated with micellar drug delivery systems. Poly(amino acid) or its derivatives, especially poly(glutamic acid) or poly(aspartic acid) or poly(l-lysine), are widely used as micelle-forming materials because of their remarkable advantages such as easy biodegradability, good biocompatibility and availability of side functional groups. In this review, the structures, synthesis and characteristics of the amphiphilic poly(amino acid) based micelles are initially described, then the driving forces, which may determine the drug loading capacity, and the variants which affect the stability of drug-loaded micelles in blood post-injection are summarized. Furthermore, the strategies for increasing the drug loading capacity and improve the stability in blood are also described.