Biomedical Engineering Reference
In-Depth Information
have been presented by Korsmeyer and
Peppas in 1981
for poly(vinyl alcohol) (PVA) systems, and by Peppas and
Yang (1981) for PHEMA systems and their copolymers.
One of numerous examples of such swelling-controlled
systems was reported by
Franson and Peppas (1983)
,
who prepared cross-linked copolymer gels of poly-
(HEMA-
co
-MAA) of varying compositions. Theophyl-
line release was studied and it was found that near
zero-order release could be achieved using copolymers
containing 90% PHEMA.
previously unreported dependence between the cross-
link density and protein diffusion coefficient and the
initial molecular weight of the linear PEGs.
Lowman
et al.
(1997)
have presented an exciting new
method for the preparation of PEG gels with controllable
structures. In this work, highly cross-linked and tethered
PEG gels were prepared from PEG dimethacrylates and
PEG monomethacrylates. The diffusional behavior of
diltiazem and theophylline in these networks was stud-
ied. The technique presented in this work is promising
for the development of a new class of functionalized
PEG-containing gels that may be of use in a wide variety
of drug delivery applications.
PVA
Another hydrophilic polymer that has received attention
is PVA. This material holds tremendous promise as a bi-
ological drug delivery device because it is nontoxic, is
hydrophilic, and exhibits good mucoadhesive properties.
Two methods exist for the preparation of PVA gels. In the
first method, linear PVA chains are cross-linked using
glyoxal, glutaraldehyde, or borate. In the second method,
Hassan and Peppas (2000), semicrystalline gels were
prepared by exposing aqueous solutions of PVA to re-
peating freezing and thawing. The freezing and thawing
induced crystal formation in the materials and allowed
for the formation of a network structure cross-linked
with the quasi-permanent crystallites. The latter method
is the preferred method for preparation as it allows for
the formation of an ''ultrapure'' network without the use
of toxic cross-linking agents.
Ficek and Peppas (1993)
used PVA gels for the release of bovine serum albumin
using novel PVA microparticles.
pH-Sensitive hydrogels
Hydrogels that have the ability to respond to pH changes
have been studied extensively over the years. These gels
typically contain side ionizable side groups such as car-
boxylic acids or amine groups. The most commonly
studied ionic polymers include poly(acrylamide) (PAAm),
poly(acrylic acid) (PAA), poly(methacrylic acid)
(PMAA), poly(diethylaminoethyl methacrylate)
(PDEAEMA), and poly(dimethylaminoethyl methacry-
late) (PDMAEMA). The swelling and release character-
istics of anionic copolymers of PMAA and PHEMA
(PHEMA-
co
-MAA) have been investigated. In acidic
media, the gels did not swell significantly; however, in
neutral or basic media, the gels swelled to a high degree
because of ionization of the pendant acid group.
Brannon-
Peppas and Peppas (1991)
have also studied the oscilla-
tory swelling behavior of these gels.
PEG
Temperature-sensitive hydrogels
Hydrogels of PEO and PEG have received significant
attention for biomedical applications in the past few
years (
Graham, 1992
). Three major preparation tech-
niques exist for the preparation of cross-linked PEG
networks: (i) chemical cross-linking between PEG
chains, (ii) radiation cross-linking of PEG chains, and (iii)
chemical reaction of mono- and difunctional PEGs. The
advantage of using radiation-cross-linked PEO networks
is that no toxic cross-linking agents are required. How-
ever, it is difficult to control the network structure of
these materials.
Stringer and Peppas (1996)
have pre-
pared PEO hydrogels by radiation cross-linking. In this
work, they analyzed the network structure in detail.
Additionally, they investigated the diffusional behavior of
smaller molecular weight drugs, such as theophylline, in
these gels.
Kofinas
et al.
(1996)
have prepared PEO
hydrogels by a similar technique. In this work, they
studied the diffusional behavior of various macromole-
cules
Some of the earliest work with temperature-sensitive
hydrogels was done by
Hirotsu
et al.
(1987)
. They syn-
thesized cross-linked poly(
N
-isopropyl acrylamide)
(PNIPAAm) and determined that the LCST of the
PNIPAAm gels was 34.3
C. Below this temperature,
significant gel swelling occurred. The transition about this
point was reversible. They discovered that the transition
temperature was raised by copolymerizing PNIPAAm
with small amounts of ionic monomers.
Dong and
Hoffman (1991)
prepared heterogeneous gels containing
PNIPAAm that collapsed at significantly faster rates than
homopolymers of PNIPAAm.
Yoshida
et al.
(1995)
and
Kaneko
et al.
(1996)
developed an ingenious method to
prepare comb-type graft hydrogels of PNIPAAm. The
main chain of the cross-linked PNIPAAm contained
small-molecular-weight grafts of PNIPAAm. Under con-
ditions of gel collapse (above the LCST), hydrophobic
regions were developed in the pores of the gel resulting in
in
these
gels.
They
noted
an
interesting,
yet
