Stimuli-Responsive Lipid -Based Self-Assembled Systems - Self-Assembled Supramolecular Architectures: Lyotropic Liquid Crystals - page 266

temperature change to reversibly modify drug release rates from the matrix
through control of the nanostructure.
The responsive phytantriol

vitamin E acetate system was taken into a
proof-of-concept in vivo study in rats. The subcutaneous injection of the liquid
crystal matrix and subsequent application of a heat or cool pack to the site of
injection provided control over the matrix nanostructure, which consequently
modifi ed drug absorption from the implanted delivery system in vivo. Along
similar lines, the phase transformation of vesicles to nonlamellar phase struc-
tures has also been proposed as a means to stimulate drug release from self-
assembled lipid systems. One such system is monoelaidin as it is known to
undergo a lamellar-to-cubic phase transition at physiological temperatures
(Yaghmur et al., 2008a).
However, practicalities of using direct heat as the stimulus will likely limit
the ultimate development of such a system as the basis of an actual product.
The use of temperature as a stimulus would be limited to applications where
the site of required treatment is readily accessible and amenable to direct
heating or cooling, essentially limiting applicability to subcutaneous depot
application. Further problems arise when one considers that the body encoun-
ters local temperature changes in everyday situations, such as a hot shower,
leaning against cold surfaces, and the like, with potential to lead to accidental
activation. Hence more selective means of inducing hyperthermic conditions
are desirable, and one possible solution is considered when discussing photo-
thermal activation later.

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9.3.2.2 Light Light-responsive systems have the advantage of being non-
invasive and provide a broad range of adjustable parameters such as wave-
length, duration, and intensity that can be optimized in a nondisruptive manner.
Light-sensitive self-assembling systems have been reviewed recently (Eastoe
and Vesperinas, 2005) as have light-activated drug delivery systems (Alvarez-
Lorenzo et al., 2009; Shum et al., 2001). The photoactivation mechanism in
self-assembled systems can be distributed into three categories: photochro-
mics, irreversible photoactivation, and photothermal, each of which are dis-
cussed further below.

Photochromic Systems Photochromic molecules reversibly isomerize on
exposure to a light source, in most cases in the UV-visible range. When
incorporated into a self-assembled system, the activation and deactivation of
photochromics cause a steric disturbance in the packing in the self-assembled
structures resulting in a change in, for example, drug release. The response
of the lipid system can be manipulated by the composition of the lipid host
and photochromic concentration (Bisby et al., 1999a,b). Research into pho-
tochromic self-assembled systems has focused on azobenzene and spiropyran
moieties among others (Eastoe and Vesperinas, 2005). In some cases, photoi-
somerization does not compromise interface integrity, and a pulsatile delivery
may be achieved (Khoukh et al., 2005; Tong et al., 2005; Zhang et al., 2009).