Biomedical Engineering Reference
In-Depth Information
interaction between the ionic segment of the block polymer and the surfac-
tant group changes these segments from water-soluble to water-insoluble,
leading to a hydrophobic core in the micelles [107]. MNPs can be engi-
neered by means of ligand coupling, or addition of pH-sensitive moieties,
according to the biological characteristics of the diseased site for active tar-
geting. All these features related to MNPs make them ideal carriers for anti-
cancer drugs and tumor targeting [108]. On reaching the target site, micelles
are internalized into the cells via fluid-state endocytosis. To overcome per-
meability problems, amphiphilic copolymers are used to encapsulate poorly
water-soluble anticancer drugs in MNPs. These have an inner core made
up of hydrophobic block copolymer in which the drug becomes entrapped,
and an outer shell of hydrophilic block copolymer that reduces the interac-
tions of drugs with the outer aqueous environment, keeping them stable.
The hydrophilic outer part can be made up of polyethers like PEG, and
poly(ethylene oxide) (PEO). Other hydrophilic shells are made up of poly-
mers such as poly(acryloylmorpholine), poly(trimethylene carbonate), and
poly(vinylpyrrolidone). Genexol-MNP is the first non-targeted polymeric
micellar formulation approved for cancer therapy. It is currently being evalu-
ated in a clinical phase II trial in the USA for metastatic pancreatic cancer
therapy. The clinical phase II results showed ~30% of the patients had a
stable disease status and 60% of the patients had an increased survival of
one year [109].
Many recent studies have revealed that polymer-conjugated drugs and
nanoparticles show prolonged circulation in the blood followed by passive
accumulation in tumors, even in the absence of targeting ligands, demon-
strating the existence of a passive retention mechanism. Tumor vasculature
showed a high proportion of proliferative endothelial cells, increased tortu-
osity and aberrant basement membrane formation. These features render
tumor blood vessels permeable to macromolecules. Thus, numerous studies
have shown, that the EPR effect causes passive accumulation of macromol-
ecules and NPs in solid tumor, enhancing the therapeutic index while de-
creasing side effects. Active targeting aims to increase the drug delivery to
the target utilizing biologically specific interactions such as antigen-antibody
binding or locally applied signals such as sonication or heating. Active tar-
geting makes use of characteristics shown by the tumor cells, such as over-
expression of cell surface tumor-associated antigens that are at low levels in
normal tissue cells, as well as of the tumor specific antigens and the relatively
more acidic nature of tumor compared to normal tissue. Active targeting de-
creases adverse side effects, because the drug accumulates only in the tumor
sites, and it allows cellular uptake of the drug through endocytosis.
Surfactants are being incorporated into anticancer metal-based drugs.
The surfactant dodecyl amine reacts with selenious acid to produce a qua-
ternary ammonium salt, which can be conjugated to copper or cobalt ions
to form copper or cobalt cationic complexes. Initial studies demonstrated
