**2. Drug Delivery**

## *2.1. Stereocomplexed Micelle System*

Micelles exhibiting specific core–shell structures are widely applied in drug delivery systems, because they can load a variety of drugs owing to their good loading capacity. Furthermore, micelles have a higher thermodynamic stability than colloids under physiological conditions owing to the lower critical micelle concentration. Therefore, polymeric micelles induced by the self-assembly of amphiphilic block copolymers have been vigorously researched for their biomedical roles, such as target-specific carriers, nano-bioreactors, and non-viral gene vectors. However, polymeric micelles have limited applications because of a short circulation time, due to their rapid excretion via urine after intravenous injection, and difficulty in accumulation and providing sustainable drug release at the target site [18]. Strategies for chemical cross-linking of hydrophilic poly(ethylene glycol) (PEG) segments have been proposed since the 1990s to improve the stability of polymeric micelles. Gref et al. (1994) fabricated nanospheres composed of a core and shell formed by biodegradable polymers, such as poly(lactic co-glycolic acid) (PLGA), polycaprolactone (PCL), and their copolymers, covalently bonded with PEG [19]. The PEG coating could significantly increase the blood circulation time of carriers by reducing their detection and opsonization by macrophages in the reticuloendothelial system and decrease their accumulation in the liver. In addition, this injectable nanoparticle carrier could encapsulate up to 45% of its weight in a one-step procedure. Micelles induced by biodegradable polymers enable the control of drug release kinetics and time, as the degradation period varies with the molecular weight (*Mn*) of the polymer. Furthermore, this feature allows higher kinetic and thermodynamic stabilities than those of a surfactant micelle with a lower molecular weight [20]. Kang et al. reported that monodisperse stereocomplexed micelles could be obtained by self-assembly of the PLA-PEG block copolymer [21]. This report was the first to verify that PLA-based micelles can form stereocomplex configurations in aqueous conditions. The micelles exhibited improved kinetic stability, as well as both physical and chemical stabilities. In particular, secondary aggregation, which is known to be the main problem of conventional polymeric micelles, was reduced. Figure 1a shows an atomic force microscopy (AFM) image of a stereocomplexed micelle with a spherical shape of approximately 46 nm diameter and a narrow size distribution. Figure 1b indicates that the micelle has a normal X-ray diffraction (XRD) pattern and a small crystalline domain of sc-PLA.

**Figure 1.** (**a**) AFM image of stereocomplexed micelle induced by mixing of PEG-*b*-PDLA72 and PEG-*b*-PLLA73 at equal proportions. (**b**) XRD patterns of PEG-*b*-PLA films (**i**) and stereocomplexed micelles composed of equimolar amounts of PEG-*b*-PDLA72 and PEG-*b*-PLLA73 (**ii**) [21], Copyright 2005. Reproduced with permission from the American Chemical Society.
