Amphiphilic Block Copolymer Based Nanocarriers for Drug and Gene Delivery - Intracellular Delivery: Fundamentals and Applications - page 281

induced cytotoxicity in MDA435/LCC6 cells, pointing to the potential of RGD/
TAT-functionalized virus-like micelles as promising carriers for efficient delivery to
reverse the P-gp mediated multidrug resistance.

4 Polymeric Micelles for Nonparental Drug Administration

Research on the potential benefit of polymeric micelles in improving the absorption
and bioavailability of drugs through non-intravenous routes of administration is in
its infancy (Bromberg 2008 ; Malik et al. 2007 ). Polymeric micelles can enhance the
oral absorption of encapsulated drugs in different ways (Mathot et al. 2006 ; Sant
et al. 2005 ) including an increase in the apparent solubility of hydrophobic drugs;
protecting the encapsulated drug against degradation in gastrointestinal tract;
prolonging drug residence time through insertion of mucoadhesive shells, facilitating
the transport of the encapsulated drug through the epithelial barrier by fluid phase
endocytosis; bypassing or inhibiting the efflux pumps; and targeting specific carriers
for receptor mediated transport. In addition to oral route, attention has been paid to
the application of polymeric micelles through transdermal and ocular administra-
tion (Tu et al. 2007 ; Liaw and Lin 2000 ; Gupta et al. 2007 ). Pluronic F-127, has
been widely used to provide a transdermal delivery through enhancement of pene-
tration in the stratum corneum and the viable epidermis layer (Ruiz et al. 2007 ).
The utility of Pluronic F127 for ocular delivery of pilocarpin has also been assessed
(Desai and Blanchard 1998 ).

5 Concluding Remarks and Perspectives

In this chapter, we provided an update on several chemical strategies used to
enhance the properties of nanoscopic core/shell structures formed from self assembly
of ABCs, namely polymeric micelles. Clearly, versatility of polymer chemistry in
ABCs provides unique opportunities for tailoring polymeric micelles for optimal
properties in gene and drug delivery. Chemical modification of the polymer structure
in the micellar core through introduction of hydrophobic or charged moieties, con-
jugation of drug compatible groups, core cross-linking has led to enhanced stability
for the micellar structure and sustained or pH-sensitive drug release. The modifica-
tion of polymeric micellar surface with specific ligands (carbohydrates, peptides,
antibodies) have shown benefit in enhancing the recognition of carrier by selective
cells leading to improved drug and gene delivery to the desired targets. Importantly,
their self-assembly nature in aqueous environment offers the opportunity to scale-up
the production of the micelle formulation to meet potential clinical application.
Despite that the importance and benefit of chemical flexibility of block copoly-
mers in improving the delivery properties of polymeric vesicles can also be envi-
sioned, research in drug delivery by polymeric nanocarriers is still in its infancy.