Biomedical Engineering Reference
In-Depth Information
Solid polymer
Cell-targeting
surface
modification
A
C
Entrapped solid drug
Fibrous
Polymer
sponge
Polymer shell
Encapsulated drug
solution
B
Drug within pore
spaces or drug within
polymer fibers
D
FIGURE 5.18 Polymers provide a versatile matrix for controlled release of drugs and biomolecules. Pharma-
ceutical agents can be contained within microparticles, microcapsules, or porous polymer blocks or conjugated
to single chains of polymer. Drug targeting can be accomplished through the use of cell-specific ligands.
the rate of protein/drug release decreases. Polymer microspheres can be formed around
drug solutions, thereby encapsulating the drug as another means of preparing a con-
trolled-release formulation. Polymers that undergo bulk erosion tend to have burst release
rates as compared to polymers that undergo surface erosion. The targeting of a drug to a
particular cell type can be accomplished by using cell-specific ligands. Microparticles that
have been modified with ligands do not diffuse uniformly throughout the body. Instead,
the drug is delivered directly to only certain cell types through a receptor-ligand interaction.
For example, liposomes have been prepared with folic acid ligands that are preferentially
taken up by cancer cells because cancer cells express more folate receptors than do other
cell types.
Direct injection of the drug into the targeted tissue is another means of obtaining high
local drug concentrations. Controlled release of the drug at the site is accomplished through
conjugation of the drug to a biomaterial drug delivery vehicle. This is particularly useful
when the drug has toxic side effects that can be minimized by exposing only the tissue of
interest to high drug levels. With local drug delivery, the toxic peak blood levels of drug
are reduced, and there are sustained levels of active drug over a longer time period, leading
to better efficacy (Figure 5.19). As an alternative to direct injection, chemotherapy-carrying
magnetic particles (magnetoliposomes) also have been developed. After systemic injection,
the drug-loaded particles are then localized to the cancer site by guidance with magnets.
Some drugs do not need to be solubilized to initiate biological activity. For example,
nerve growth factor is effective when immobilized on a surface. Even higher levels of activ-
ity may be obtained after immobilization of a protein onto a surface due to conformational
changes that occur upon immobilization. The active portions of the protein may be better
exposed after immobilization. Alternatively, all biological activity may be lost after immobi-
lization, so it is always necessary to conduct separate tests to confirm drug activity after
immobilization or conjugation to a biomaterial surface.
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