Biomedical Engineering Reference
In-Depth Information
contrast, if the vehicles in the blood stream are able to traverse tumors, they
are assumed to possess an order of magnitude smaller hydrodynamic diameter
than the openings of the vessels. Therefore, a broad group of features in the
macromolecular architecture, such as its molecular weight, molecular
conformation, chain flexibility, branching, and location of the attached drug,
have a great impact on the elimination of polymeric carriers through the
kidney, while the architectural factors have a much smaller effect on the
extravasation of the drug delivery systems into the tumor tissues. 42 From
the structural perspective, the molecular architecture of HBPs is prone to be
adjusted, benefiting from the various terminal groups and three-dimensional
topological architecture. Therefore, passive targeting of HBP self-assemblies
can be independently controlled in the aspects of both elimination and
extravasation. Design of HBP-based drug carriers with an effective delivery
behavior requires that the polymers must eventually be eliminated from the
body.
Hyperbranched polyglycerols (HPGs) combine several remarkable features
together, including a highly flexible aliphatic polyether backbone, multiple
hydrophilic groups, and excellent biocompatibility. Moreover, the controlled
synthesis of well-defined HPGs via SCROP of glycidol has realized the
adjustment of fundamental parameters involving molecular weight, PDI,
DB, and end-group functionality. A variety of linear-hyperbranched block
copolymers of HPBs and their assemblies with a diameter less than 200 nm
have been reported. These inherent merits of HPGs and their assemblies are
useful for a number of biomedical applications, such as drug encapsulation or
surface attachment. 43,44 The backbone of HPGs often appears in the drug
delivery systems with a passive targeting ability. Similarly, if other HPB self-
assemblies have a suitable diameter, they can take advantage of the EPR effect
to transport drug or gene cargo and manifest the preferential accumulation to
tumor tissues.
d n 4 y 3 n g | 1
5.3.2.2 Active Targeting
One major limitation with passive targeting is that it is hard to realize a
sufficiently high level of drug concentration at the tumor site, resulting in low
therapeutic efficacy and triggering severe side effects. To further improve the
drug delivery efficiency and cancer specificity, a strong emphasis has been put
on exploiting nanoparticles with active tumor-targeting ability. Active
targeting can be achieved by functionalizing nanocarriers with targeting
ligands such as small molecules (e.g. folic acid and saccharide), antibodies,
lectin, and peptides. These functional components can recognize and bind to
specific receptors that are unique to cancer cells. Non-immunogenic folic acid
(FA) possesses a high affinity for FA-binding proteins that are selectively
overexpressed on the surface of human tumor cells, including breast, lung,
brain, endometrial, renal, and colon cancer cells. Since the FA receptor is
frequently overexpressed in tumor cells, the experimental results from flow
 
Search WWH ::




Custom Search