Biomedical Engineering Reference
In-Depth Information
shown good drug retention in the liposomal formulation. In experimental
studies, such systems showed significant improvements in tumor size re-
duction working through the EPR mechanism. Recently, Chytil et al. [60]
have exploited the EPR effect for targeting HPMA copolymer-based drug
carriers with covalently bound hydrophobic substituents for targeting solid
tumors. Treatment of mice bearing EL-4 T-cell lymphoma with the above
conjugates resulted in significant tumor regression. These nanoconjugates
also enhanced tumor accumulation, indicating an important role of the EPR
effect in excellent anticancer activity of the conjugate. Since most therapeu-
tics agents do not present intrinsic affinity to cells, coupling them to carri-
ers with affinity properties provides advantages. Hydrophilic and slightly
positively-charged polymers provide affinity to the negatively-charged
plasma membrane of cells [51].
Direct intratumor delivery of anticancer agents using NPs can be used
in the treatment of local cancers such as prostate, head and neck cancers.
Recently, Sahoo et al. [61] have demonstrated that transferrin (Tf ) conju-
gated paclitaxel (Tx)-loaded biodegradable NPs are more effective in dem-
onstrating the antiproliferative effect of the drug than its solution or with
un-conjugated Tx-loaded NPs. NPs are emerging as a promising tool for
the intracellular delivery of practically insoluble drugs and sensitive drugs.
Intracellular targeting refers to the delivery of therapeutic agents to specific
compartments or organelles within the cell, and the delivered cargoes must
gain access to intracellular compartments where their molecular targets are
located. Interventions related to RNA interference or delivery of antisense
oligonucleotides requires transport of these cargoes to the cytosol of the
cell.
Gene therapy is a promising new approach for treating a variety of ge-
netic and acquired diseases. These macromolecules are unstable and show
a poor cellular uptake and are rapidly degraded by nucleases. To overcome
these limitations, various chemical modifications of oligonucleotides have
been tried. These modifications have disadvantages such as decreased
mRNA hybridization, elevated cytotoxicity, and increased nonspecific tar-
geting. In order to overcome the disadvantages of viral carriers (high cyto-
toxicity, cost, small transgene size), nonviral carriers have been developed.
The advantages associated with nonviral carriers include facile large scale
manufacture, low immunogenic response, versatile modifications, and the
capacity to carry large inserts. Gene therapies require delivery to the cytosol,
with subsequent transport to the cell nucleus. The drug can be delivered into
target cells by simple diffusion, or it may involve complex cellular machinery.
The major route of intracellular therapeutic uptake is through endocytosis.
This strategy is ideal in the case of delivery of therapeutic agents whose ac-
tion is required at said sub-cellular compartments, such as in the case of
carrier-assisted delivery of enzyme replacement for lysosomal storage dis-
orders. Carriers themselves can also be designed to overcome endosomal
