Biomedical Engineering Reference
In-Depth Information
achieve cancer-targeted drug delivery is the utilization of unique molecular markers overexpressed
at the cancerous tissues. Antibodies and specifi c ligands are good candidates for such a purpose.
Recently, two studies have demonstrated that either monoclonal antibody or peptide ligand can
be deposited onto polyelectrolyte capsule surface with successful
in vitro
targeting. Suslick group
chose a small tripeptide turn sequence arginine-glycine-aspartic (RGD) as the targeting ligand,
which recognizes highly expressed αVβ3 receptors on tumor endothelial cells [165]. Different pep-
tides with an RGD motif embedded at the ends or in the middle of a highly positively charged,
polylysine sequence were synthesized: at the amino terminus, RGDKKKKKK; in the middle,
KKKKRGDKKK; and at the carboxy terminus, KKKKKKKRGD. An additional decapeptide
polylysine K10 was prepared as a control. The positively charged lysine residues electrostatically
secure the RGD motif to the surface of the microspheres. Human colon tumor cells (HT29), over
expressing of integrins, were used to test the effi cacy of the RGD-modifi ed microspheres in tumor
targeting. The fl uorescence microscopy revealed that binding of RGD-modifi ed microspheres is
increased relative to the unmodifi ed ones, especially the RGDKKKKKK peptides exhibit the best
binding to the tumor cells, with the KKKKRGDKKK peptide binding the least. In the other study
led by the Caruso group, humanized A33 monoclonal antibody (HuA33 mAb), labeled on LbL
shells, were tested to recognize A33 antigen-expressing LIM1215 colorectal cancer cells
in vitro
[166]. Both fl ow cytometry and fl uorescence microscopy studies showed increased cell binding of
shells tagging with HuA33 mAb. To determine the effectiveness of polyelectrolyte capsules as novel
colloidal delivery systems,
in vivo
targeting experiment is necessary.
10.4
POLYMERIC MICELLES FOR DRUG AND GENE DELIVERY
10.4.1 I
NTRODUCTION
In recent years, nano-sized particles have been receiving much attention in the fi eld of drug delivery
systems because of their special drug-loading abilities and their unique distribution characteristics
in the body. Polymeric micelles, formed by the self-assembly of either amphiphilic or oppositely
charged copolymers in aqueous solution, are one of the most studied nanocarriers for both drug and
gene del iver y appl icat ions. T These m icel les have cha racter ist ic core - shel l a rch ite ct u re a nd, genera l ly,
narrow size distribution. In the micelles, hydrophobic or oppositely charged segments aggregate
because of either the hydrophobic interaction or the electrostatic interaction to form an inner core,
while the shell of the micelles is formed by a hydrophilic segments that are covalently connected
with the core segments. Hydrophobic drugs or ionic compounds are loaded through hydrophobic
interaction or electrostatic interaction into the core of the micelles, which are surrounded by the
hydrophilic corona that barrier the contact of the drug with the surrounding environments. The dis-
tribution of the drug-loaded micelles in the body are thus mainly determined by the size of the
micelles and also the surface properties of the micelles shell, but less infl uenced by the nature
of the loaded drug.
The use of nano-sized polymeric micelles as drug carriers has many advantages. These particles
are ultrafi ne sized; thus, they can penetrate the capillary and move to desired place inside the body.
They are of high-loading capacity, and, particularly, they are powerful vehicles that provide a par-
ticular mechanism to disperse water-insoluble drugs into aqueous media.
10.4.2 A
MPHIPHILIC
B
LOCK
C
OPOLYMER
M
ICELLES
:
PEO-PPO-PEO B
LOCK
C
OPOLYMER
(P
LURONIC
)
Among the polymeric micelles, those composed of the amphiphilic block copolymers are well-
studied nanoparticles that showed high potential in drug delivery. The increasing interest in
amphiphilic block copolymer in the biomedical fi eld arises mainly because of their ability to form
micelles with core-shell architecture. The amphiphilic block copolymers are generally defi ned
