Biomedical Engineering Reference
In-Depth Information
1996
). However, below the LCST, the cross-linked gel
swells to significantly higher degrees because of the in-
creased compatibility with water.
cartilage, artificial skin, maxillofacial and sexual organ
reconstruction materials, and vocal cord replacement
materials (
Byrne
et al.
, 2002
).
Complexing hydrogels
Pharmaceutical applications
Some hydrogels may exhibit environmental sensitivity
due to the formation of polymer complexes. Polymer
complexes are insoluble, macromolecular structures
formed by the non-covalent association of polymers with
affinity for one another. The complexes form as a result
of the association of repeating units on different chains
(interpolymer complexes) or on separate regions of the
same chain (intrapolymer complexes). Polymer com-
plexes are classified by the nature of the association as
stereocomplexes, polyelectrolyte complexes, or hydrogen-
bonded complexes. The stability of the associations is
dependent on such factors as the nature of the swelling
agent, temperature, type of dissolution medium, pH and
ionic strength, network composition and structure, and
length of the interacting polymer chains.
In this type of gel, complex formation results in the
formation of physical cross-links in the gel. As the degree
of effective cross-linking is increased, the network mesh
size and degree of swelling is significantly reduced. As
a result, if hydrogels are used as drug carriers, the rate of
drug release will decrease dramatically upon the forma-
tion of interpolymer complexes.
Pharmaceutical hydrogel applications have become very
popular in recent years. Pharmaceutical hydrogel systems
include equilibrium-swollen hydrogels, i.e., matrices that
have a drug incorporated in them and are swollen to
equilibrium. The category of solvent-activated, matrix-
type, controlled-release devices comprises two impor-
tant types of systems: swellable and swelling-controlled
devices. In general, a system prepared by incorporating
a drug into a hydrophilic, glassy polymer can be swollen
when brought in contact with water or a simulant of bi-
ological fluids. This swelling process may or may not be
the controlling mechanism for diffusional release,
depending on the relative rates of the macromolecular
relaxation
of
the
polymer
and
drug
diffusion
from
the gel.
In swelling-controlled release systems, the bioactive
agent is dispersed into the polymer to form nonporous
films, disks, or spheres. Upon contact with an aqueous
dissolution medium, a distinct front (interface) is ob-
served that corresponds to the water penetration front
into the polymer and separates the glassy from the rub-
bery (gel-like) state of the material. Under these condi-
tions, the macromolecular relaxations of the polymer
influence the diffusion mechanism of the drug through
the rubbery state. This water uptake can lead to con-
siderable swelling of the polymer with a thickness that
depends on time. The swelling process proceeds toward
equilibrium at a rate determined by the water activity in
the system and the structure of the polymer. If the
polymer is cross-linked or if it is of sufficiently high
molecular weight (so that chain entanglements can
maintain structural integrity), the equilibrium state is
a water-swollen gel. The equilibrium water content of
such hydrogels can vary from 30% to 90%. If the dry
hydrogel contains a water-soluble drug, the drug is es-
sentially immobile in the glassy matrix, but begins to
diffuse out as the polymer swells with water. Drug re-
lease thus depends on two simultaneous rate processes:
water migration into the device and drug diffusion out-
ward through the swollen gel. Since some water uptake
must occur before the drug can be released, the initial
burst effect frequently observed in matrix devices is
moderated, although it may still be present. The con-
tinued swelling of the matrix causes the drug to diffuse
increasingly easily, ameliorating the slow tailing off of the
release curve. The net effect of the swelling process is to
prolong and linearize the release curve. Details of
hydrogels for medical and pharmaceutical applications
Applications
Biomedical applications
The physical properties of hydrogels make them attrac-
tive for a variety of biomedical and pharmaceutical ap-
plications. Their biocompatibility allows them to be
considered for medical applications, whereas their hy-
drophilicity can impart desirable release characteristics
to controlled and sustained release formulations.
Hydrogels exhibit properties that make them desir-
able candidates for biocompatible and blood-compatible
biomaterials (
Merrill
et al.
, 1987
). Nonionic hydrogels
for blood contact applications have been prepared from
poly(vinyl alcohol), polyacrylamides, PNVP, PHEMA,
and poly(ethylene oxide) (PEO) (
Peppas
et al.
, 1999
).
Heparinized polymer hydrogels also show promise as
materials for blood-compatible applications (
Sefton, 1987
).
One of the earliest biomedical applications of hydrogels
was in contact lenses (
Tighe, 1976; Peppas and Yang,
1981
) because of their relatively good mechanical stability,
favorable refractive index, and high oxygen permeability.
Other potential applications of hydrogels include
(
Peppas, 1987
) artificial tendon materials, wound-healing
bioadhesives,
artificial
kidney
membranes,
articular
