Amphiphilic Block Copolymer Based Nanocarriers for Drug and Gene Delivery - Intracellular Delivery: Fundamentals and Applications - page 267

Fig. 11 Aggregation of PNiPAAm-PSt micelle due to hydrophobic surface association above the
LCST

buffered saline were used for targeted DOX delivery (Chung et al. 2000 ;
Kohori et al. 1999 ). Micelles released five times more DOX at 42.5°C than 37°C.
DOX-loaded micelles did not show much cytotoxicity against bovine aorta
endothelial cells at 37°C, but showed high cytotoxicity at 42.5°C.

2.3 Ligand Decorated Polymeric Micelles for Active Targeting

Monoclonal antibodies (mAb)s - Chemical conjugation of mAbs or their Fab
fragments to the shell of polymeric micelles can produce immunomicelles. Kabanov
et al. developed Pluronic P-85 micelles conjugated to murine polyclonal antibody
against a 2 glycoprotein (a 2 -GP) to deliver neuroleptic agent haloperidol to brain
(Kabanov et al. 1989 ). Antibody C225 against epidermal growth factor receptors was
coupled to the terminus of a DOX-bound PEO-P(L-Glu) and showed enhanced cyto-
toxicity on A431 cells compared to free DOX (Vega et al. 2003 ). Torchilin et al.
developed tumor-targeted phosphalipid-based immunomicelles by chemical conjuga-
tion of mAb 2C5 and 2G4 to the micellar surface. PXT-loaded 2C5-immunomicelles
exhibited a superior efficiency compared to PXT-loaded plain micelles or free drug
against human breast cancer MCF-7 cells in vitro . 111 In-labeled 2C5 immunomicelles
revealed significantly higher accumulation in LLC tumor-bearing mice than plain
micelles. Accordingly, PXT loaded 2C5 immunomicelles exhibited higher drug accu-
mulation in LLC tumors in mice which resulted in higher therapeutic efficacy com-
pared to free PXT and PXT-loaded in plain micelles (Torchilin et al. 2003 ).

Carbohydrates - Polymeric micelles decorated with glucose, galactose, mannose
and lactose have been reported (Choi et al. 1998 ; Jule et al. 2003 ; Nagasaki et al.
2001 ). Carbohydrate receptors like asialoglycoprotein (ASGP) on hepatocytes and
mannose receptors on kupffer and liver endothelial cells are known to play a crucial