Application of MEMS in Drug Delivery 145
tems to achieve the desired constant drug release profile. Several successful
approaches have been commercialized in the past decade, notably Gliadel®,
poly(anhydride) wafers that release Carmustine (BiCNU®) at a constant rate asthe
polymer degrades, developed for the treatment of malignant brain tumors. An
additional example is Norplant® which contains an anti-contraceptive drug that
is being released at a constant rate via diffusion, as the polymer rods containing
the drug depot degrade over time.
The technological development presently permits the access to delivery
devices which ensure a constant drug release. Thus, expectations of addressing the
more complex pulsatile and dynamic mode drug delivery set the stage for the next
technological development in drug delivery. These needs are rooted into clinically
relevant treatment regiments. Once more, the technological development took
advantage of known polymeric systems and their properties to fulfill such need.
Advances related to discretely modulating a polymer’s mechanical properties in
response to external stimuli such as change in electric or magnetic fields, exposure
to ultrasound, light or enzymes, and changes in pH or temperature have lead to
some success.
5,6
Unfortunately, several limitations to complete control over the
release regiment must be noted:
(a) stimuli application usually leads to a “burst” in drug release, yet, removal of
the source does not stop the release completely,
(b) in some cases, technology has not been capable of miniaturizing the stimulus
source or such source might be too expensive for the development of a com-
mercially viable device,
(c) the need for a completely implantable rather than trans-cutaneous drug deliv-
ery system which has the capability of delivering in a controlled and dynamic
manner a desired and complex drug regiment over extended periods of time
eludes the present technological reality.
Langer’s research group at Massachusetts Institute of Technology (MIT) has
assumed an active role in advancing a viable solution to such complex require-
ments. Their technological strides have materialized into using microfabrication
technology to initiate the development of an implantable multi-array BioMEMS
which allows for remotely activated release of complex drug regiments.
7.1.3 The Host-device Continuum
A fundamental requirement for any in vivo implantable drug delivery system is its
reliable performance over time. A plethora of biomaterials and mechanical devices
have been successfully implanted in the body for decades.
79
The development of
biomaterials for in vivo use is proof of the ability of the body to tolerate long-term
implants of non-living materials, under certain circumstances. But, in the case of
BioMEMS, tolerance of the device, otherwise known as biocompatibility, repre-
sents only one aspect of the required biological performance. Normal biological
reactions such as protein adsorption, cellular adhesion, and fibrous encapsulation
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