Biomedical Engineering Reference
In-Depth Information
4.1.3 Nanoparticle targeting
One of the major challenges in drug delivery is to carry the drug at the place
where it is needed and to avoid potential side effects on non diseased organs.
After reaching the targeted tissue, drugs should have the ability to selec-
tively kill diseased cells without affecting normal cells. These basic strategies
are also associated with improvements in patient survival and quality of life
by increasing the intracellular concentration of drugs and reducing dose-
limiting toxicities simultaneously. In some cases, general enhanced delivery
throughout the body, rather than specific delivery to particular organs, is
preferred. This is the case for genetic conditions that affect multiorgan sys-
tems due to ubiquitous distribution of the molecular markers or functions
affected, such as in many monogenic disorders with both peripheral and
central nervous system components. Targeted drug delivery can be achieved
by active targeting of the drugs, or through passive targeting to the site of
action. Active targeting requires the therapeutic agent to be achieved by con-
jugating the therapeutic agent or carrier system to a tissue or cell-specific
ligand [57]. The success of drug targeting depends on the selection of the
targeting moiety, which should be abundant, have high affinity and specific-
ity of binding to cell surface receptors, and should be well suited to chemi-
cal modification by conjugation. The active targeting can be achieved by
molecular recognition of the diseased cells by various signature molecules
over-expressed at the diseased site, either via the ligand-receptor, antigen-
antibody interactions or by targeting through aptamers. The therapeutic
agent can be actively targeted by conjugating the carrier with a cell or tissue-
specific ligand, thereby allowing a preferential accumulation of the drug at
the diseased site. PEGylated gold NPs are decorated with various amounts
of human Tf by Choi et al. [58] to enhance active targeting. Their results
suggest that targeted NPs can provide greater intracellular delivery of thera-
peutic agents to the cancer cells within solid tumors than their non-targeted
analogs.
Passive targeting exploits the anatomical differences between normal and
diseased tissues to deliver the drugs to the required site, because the physiol-
ogy of diseased tissues may be altered in a variety of physiological conditions
through the enhanced permeability and retention (EPR) effect [59]. The
difference between infection-induced EPR effect and that of cancer is the
duration of the retention period. The retention in normal tissue, where in-
flammation occurs, is shorter than with cancer because the lymphatic drain-
age system is still operative. The EPR effect has been greatly exploited for
delivering various therapeutics at the site of action, and many studies po-
tentially support this mechanism of passive targeting. Drugs encapsulated
in nanoparticles or drugs coupled to macromolecules can passively target
tumors through the EPR effect. One of the examples is Doxil, a sterically
stabilized PEGylated liposome that encapsulates doxorubicin. Doxil has
