Biomedical Engineering Reference
In-Depth Information
bullet. Helmut Ringsdorf suggested a standard model that could be used to
improve targeted drug delivery by focusing on different components of the
polymer to give abilities for imaging, targeting, and drug loading.
6
The
Ringsdorf model has been an inspiration for many polymer designs in drug
delivery for cancer therapy.
7
It has led to a trend of polymer therapeutics, with
researchers devising various ways to give properties to polymers. The
versatility in chemistry and molecular architecture is one of the advantages
of polymers in targeted drug delivery. With polymer therapeutics and the
newly emerging field of nanomedicine, the possibilities are only limited by
one's imagination.
Comparative PubMed searches show an exponential increase in the number
of articles related to polymer therapeutics and nanomedicine.
8
Companies are
willing to invest large amounts for research and development of these
products because of their potential to return large profits. Review articles list
various targeted drug delivery approaches that are in clinical trials, which
include polymer-drug conjugates, monoclonal therapeutics, some that
specialize in multidrug resistance, and those classified as nanoparticle-based
therapeutics.
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1.2 Current Paradigm
The current paradigm associated with targeted drug delivery shapes the design
of the drug carriers. Currently, there are certain properties thought to
maximize drug delivery to the tumor. First, a stable carrier for the drug can
help reduce side effects and increase the therapeutic effect. A stable carrier will
mean that the drug is protected from the body and that normal (nontargeted)
tissues are protected from the drug. Second, the carrier will accumulate in the
tumor via the enhanced permeability and retention (EPR) effect. Third, the
carrier
can
target
the
tumor
based
on
both
environmental
and
cellular
components.
In order to arrive at the tumor, the drug needs a stable carrier. The majority
of anticancer drugs are hydrophobic and do not dissolve in aqueous solutions.
The first requirement of a stable carrier is simply the ability to carry the drug.
As the carriers transport the drug, they need to form a stable barrier between
the drug and the body. Protecting the body from the drug requires that the
drug not interact with nontargeted cells, tissues, or organs. Protecting the drug
from the body provides long circulation in the bloodstream. Increasing the
blood circulation half-life of the carrier can increase chances of interactions
with the target. To achieve long blood circulation, it needs to avoid interaction
with the reticuloendothelial system (RES), also known as the mononuclear
phagocyte system (MPS). Cell uptake by the MPS will decrease the efficacy of
the treatment. There should also be protection against blood-borne proteins
that would lead to inactivation, destabilization, or opsonization. The carrier
should also be designed to limit accumulation in the kidney, liver, spleen, and
other non-targeted organs. Administration of the chemotherapeutic agent
