Biomedical Engineering Reference
In-Depth Information
However, PEG is not a biodegradable polymer and so we will not explore the
mechanism of action of these conjugates further.
There are a number of polymer-drug conjugates that do contain biodegradable
components. One key function of polymer-drug conjugates is their ability to
release the drug once it has been carried into the cell by the polymer component.
The high molecular mass of the polymer-drug conjugate results in an accumula-
tion of the conjugate in certain types of tumors. This accumulation is caused by
the enhanced permeability and retention effect, whereby many tumors possess
leaky blood vessels that allow the conjugate to escape the blood system effi ciency.
In contrast, nontumor sites within the body have less-leaky blood vessels and so
the drug does not enter tissues within which it would cause major side effects.
Within the tumor site, the polymer-drug conjugate is taken up by cells and enters
intracellular vesicles called lysosomes. The drug must escape the lysosome to have
a pharmacological effect.
The Duncan group has described polymer-drug conjugates that preferentially
release drug within the lysosome [38]. These lysosomotropic nanomedicinces use
N
- (2 - hydroxypropyl)methacrylamide copolymer as the nondegradable backbone of
the conjugate. This copolymer has been shown to be nontoxic and nonimmuno-
genic. The linkage between the
N
- (2 - hydroxypropyl)methacrylamide copolymer
and the anticancer drug is chemically broken within the lysosome when the pH
falls. Hence, the drug remains as part of the conjugate until it has been success-
fully delivered to the target cell.
15.6.6
Responsive Polymers for Injectable Delivery
Responsive polymers undergo a phase change or gelation in result of a change in
local environmental conditions. This concept has been used to great success in
the development of block copolymers of PLGA - PEG - PLGA [39] . A product called
ReGel is being developed for a range of drug delivery applications by exploiting
the thermal gelation of this class of polymers. Gelation occurs at a temperature
just below the body temperature. As a result, aqueous solutions of PLGA-PEG-
PLGA are liquid at room temperature and may be injected through syringe needles
into the body. Within the body, the system rapidly gels to form a delivery system
that is retained at the site of administration. If a drug is included within the
aqueous polymer solution, then it will be entrapped within the gel and released
slowly due to retarded diffusion that accelerates as the PLGA component degrades.
For example, ReGel has been used to release an anticancer agent, paclitaxel, for
approximately 50 days [40] .
15.6.7
Peptide-Based Drug Delivery Systems
The remarkable properties of biological molecules within living organisms have
stimulated research into the replication of these properties in synthetic materials
