Amphiphilic Block Copolymer Based Nanocarriers for Drug and Gene Delivery - Intracellular Delivery: Fundamentals and Applications - page 256

2 Polymeric Micelles Drug Delivery

Polymeric micelles are core/shell nano-delivery systems formed through self
assembly of ABCs in an aqueous environment (Fig. 1 ). Polymeric micelles have
been widely used for solubilization of poorly water soluble drugs, depot drug
release and targeted drug delivery (Aliabadi and Lavasanifar 2006 ; Mahmud et al.
2007 ; Sutton et al. 2007 ). They have been the subject of several extensive reviews
in recent years (Croy and Kwon 2006 ; Lavasanifar et al. 2002b ; Xiong et al. 2006 ;
Osada and Kataoka 2006 ).
Among different structures, micelles consisting of poly(ethylene oxide)-
poly(propylene oxide) PEO-PPO, PEO-poly(ester)s and PEO-poly(L-amino acid)s
(PEO-PLAA) are used more extensively (Aliabadi and Lavasanifar 2006 ; Sutton
et al. 2007 ; Kwon and Forrest 2006 ). The widespread application of polymeric
micelles in drug delivery is linked to their unique core-shell architecture in which
the hydrophobic core creates a space for the encapsulation of hydrophobic drugs,
proteins or DNA; and the hydrophilic shell masks the hydrophobic core from the
biological milieu. Since hydrophilic shell minimizes protein adsorption on micelles,
polymeric micelles have the ability to evade non-specific capture by the reticuloen-
dothelial system (RES). The size of polymeric micelles is also above the threshold
of kidney filtration. Thus, polymeric micelles can lodge several types of molecules,
demonstrate prolonged circulation in blood (Nishiyama and Kataoka 2006 ; Kwon
and Forrest 2006 ; Aliabadi and Lavasanifar 2006 ; Kataoka et al. 1993 ) (Fig. 2 ), and
even get a chance for accumulation in sites with leaky vasculature (e.g., solid
tumors and inflammation sites) because of the enhanced permeability and retention
(EPR) effect (Kwon and Forrest 2006 ; Aliabadi and Lavasanifar 2006 ) (Fig. 2 ).
New blood vessels formed in tumor have large gaps in their endothelium. Some
tumor vessels even have a defective cellular lining composed of disorganized,
loosely connected, branched, overlapping, or spouting endothelial cells (Maeda 2001 ;
Maeda and Matsumura 1989 ; Muggia 1999 ). The presence of leaky vasculature at

Fig. 1 Schematic represen-
tation of the self assembly
of amphiphilic block copoly-
mers into polymeric micelles