Biomedical Engineering Reference
In-Depth Information
the drug is faster than hydrogel distention, swelling is considered to control the release
behavior. In a swelling-controlled delivery system, the drug molecules are able to diffuse
out of the rubbery phase of the polymer. Since no drug diffuses out of the glassy region of
the polymer, the drug release is related to the velocity and position of the glass-rubbery
interface [119]. A very important phenomenon of macromolecular relaxation takes place at
the glass-rubbery interface, and significantly affects the drug release of this mechanism.
Therefore, the rate of molecule release depends on the swelling rate of polymer networks.
There are many mathematical models to describe swelling-controlled release. Among
them, the Korsmeyer and Peppas model is considered to be a rigorous description [120]. In
this model, drug diffusion, polymer relaxation, and the “moving-boundary” conditions in
which the gel expands heterogeneously as water penetrates and swells the gels are all
taken into account [119,120].
6.6.1.3 Chemically Controlled Mechanisms
In addition to diffusion and swelling-controlled delivery systems, a third type of molecule
release mechanism is chemically controlled delivery. It is determined by chemical reac-
tions occurring within the gel matrix. These reactions include (1) cleavage of pendant
polymer chains via hydrolytic or enzymatic degradation; (2) reversible or irreversible reac-
tions occurring between the polymer network and releasable drug; (3) surface erosion; and
(4) bulk degradation. Among these reactions, one point that needs to be clarified is that
surface erosion may occur when the rate of water transport into the polymer is much lower
than the rate of bond hydrolysis. However, owing to the inherently high water content of
hydrogels, surface erosion only occurs in enzymatic degrading systems where the rate of
transport of enzyme into the gel is lower than the rate of enzymatic degradation.
Any of the above four reactions could be the rate-determining step and will control the
entire rate of drug release. Therefore, chemically controlled release can be further catego-
rized according to the type of chemical reaction occurring during drug release. Many
models are developed to describe the chemically controlled mechanism [117,119]. But under
certain circumstances, diffusion should also be included in the model to accurately predict
drug release.
Generally, the liberation of encapsulated or tethered drugs can occur through the degra-
dation of pendant chains or during surface erosion or bulk degradation of the polymer
backbone.
6.6.2 Drug release Stimuli
Usually, the hydrogel-based delivery systems are classified into two major categories: (1)
time-controlled systems (inert hydrogel) and (2) stimuli-induced release systems (intelli-
gent or smart hydrogel). Stimuli-induced release systems are also called “stimuli-sensitive/
responsive,” “environment-sensitive/responsive,” or “responsive” hydrogel systems. These
smart hydrogels are developed to deliver drugs in response to a fluctuating condition in a
way that desirably coincides with the physiological requirements at the right time and
proper place. Despite the huge attraction toward novel DDSs based on environment-sensi-
tive hydrogels in past and recent times, these systems have disadvantages of their own.
The most considerable drawback of stimuli-sensitive hydrogels is their significantly slow
response time, with the easiest way to achieve fast-acting responsiveness being to develop
thinner and smaller hydrogels that, in turn, bring about fragility and loss of mechanical
strength in the polymer network and the hydrogel device itself [118].
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