Page 666 - Carrahers_Polymer_Chemistry,_Eighth_Edition

Selected Topics 629

The polymer may act as a drug itself or the polymer drug may also act in both roles. Following
is a brief discussion of advantages of polymeric drugs that may apply to either mode of control
release or/and as a drug itself. Because of their size, polymers with chain lengths of about 100 units
and greater typically are unable to easily move through biological membranes, thus movement is
restricted. This can result in limiting negative side effects, such as damage to the kidneys, because
the polymer can reside in only certain body sites. Also, this limited mobility can assist in directing
the polymer drug. This also allows the use of lower and more level drug concentrations reducing
renal, kidney, and so forth damage. In some cases, multiple attachments by the same polymer chain
can be beneficial. Thus, many cancer drugs act to “tie up” the DNA chains inhibiting cell replica-

tion. Here, multiple attachments to the DNA, possible for polymer drugs that contain numerous

binding units within each single chain, might be beneficial in decreasing the cells effectiveness in
overcoming single DNA “chemical knots” (chemical bonding together of the two DNA strands).
The polymeric nature may inhibit premature drug deactivation. Thus, cisplatin (19.29), the most
widely used anticancer drug, is converted into numerous inactive, but more toxic, platinum-con-
taining compounds before it arrives at the targeted cancer cells. Placement of the active platinum-
containing platinum moiety into a polymer (19.30) decreases this tendency to hydrolyze into these
unwanted cisplatin compounds because of the greater hydrophobic character of the polymeric drug.
N NH
H 2 2
NH 3 NH 3
Pt R Pt
Cl Cl Cl Cl
Cisplatin (19.29) Polymer containing a cisplatin-like unit (19.30)

Polymers may also evade the microorganism’s defense. Recently, it was found that many cells
become drug resistant after repeated treatment. Cells have groups of molecules that protect it from
outside invasion. The small molecule drugs are considered “outside” invaders. Thus, drugs intro-
duced into their environment are considered as “outside” invaders and the cell manufactures greater
numbers of these “house-keepers” to rid the cell of the invaders. These “house-keeping” agents
are often not very specific and remove other similar drugs that intrude their cell. These “house-

keeping” proteins may not be as effective at eliminating polymer drugs.
Polymer drugs are also known to remain within human hosts longer than smaller molecules.
Depending on the illness and treatment, this preferential retention may be simply due to physical reten-
tion through entanglement with biological outer-layer materials or through some specifi c additional
interaction. Tumor-associated cells are frequently hyperpermeable to plasma proteins and other mac-
romolecules. These “leaky” vasculatures and limited lymphatic drainage, typical of tumor and missing
in normal tissue, result in the accumulation of polymers. Thus, such polymers reside in the interstitial
space of these cells. This results in enhanced permeability and retention (EPR) of large chains.
Drug design, today, typically aims at certain specific biological activities. Thus, cancer treat-

ments focus on controlling cell growth (Figure 19.6). Cell growth can be considered as occurring
in four dependent steps. Drugs are designed to control cell growth at any one of these steps directly
or indirectly. The indirect intervention of cell growth has as a target any one of the many steps that

influence the cell growth cycle. Essentially all chemo therapies are based on the continual growth
of cancer cells compared with healthy cells generally being in some rest state.
Drugs aiming to control the same problem may target different sites. For instance, in the treat-
ment of breast cancer, tamoxifen acts to control cell growth by blocking estrogen receptors on the
cancer cell while arimidex acts to reduce the body’s estrogen production.
Cancer cells have three main characteristics that are different from healthy cells. First, they are
immortal, able to replicate themselves hundreds of times while healthy cells generally replicate them-
selves less than two dozen times over our lifetime. Second, cancer cells are not contact inhibited mean-
ing that they will continue to grow forming tumors. By comparison, healthy cells replicate until they

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