Chemistry Reference
In-Depth Information
to release drug in this narrow temperature range. More recently, liposome
formulations have been modifi ed with polymers, most commonly poly(
N
-
isopropylacrylamide) or a derivative thereof, which become water insoluble
above a critical solution temperature (CST) and so destabilize the liposome
bilayer (Kono, 2001; Kono et al., 1999, 2002, 2005; Yoshino et al., 2004). Inter-
estingly, Regan and co-workers have created pore-forming amphiphiles com-
prised of cholic acid, lysine, and spermine, which act as thermal gates when
heat melts the liposome bilayer, thereby changing the release rate of glucose
in vitro (Chen and Regen, 2005; Petrov et al., 2009).
Other Thermoresponsive Structures
Reversibility of the system, that is,
the ability of the system to return to its original state on removal of the stimu-
lus, is a potentially important attribute for responsive systems for the treat-
ment of chronic conditions. Reversible activation may reduce the required
frequency of administration by providing repeat doses of drug on activation,
and switch drug release off when the stimulus is removed.
Nonlamellar liquid crystalline systems are gaining increasing attention as
potential reversible responsive materials, as the specifi c geometries adopted
by the lipids are thermodynamically stable, and transitions between structures
are generally reversible (de Campo et al., 2004). This is in contrast to most
liposomal or polymer systems where drug release behavior is often irrevers-
ible. The complexity of potential structures that may be adopted, some of
which are illustrated in Figure 9.1, also offers control over drug release rates
through the selection of specifi c amphiphile/phase structure combinations
(Lee et al., 2009a). Fong et al. (2009) have taken advantage of the reversibility
of the transition between the bicontinuous cubic (Q
2
) and inverse hexagonal
phase (H
2
) structures exhibited by the phytantriol
vitamin E acetate liquid
crystal system to switch drug release between fast and slow release rates,
respectively. Figure 9.4 shows the in vitro release of glucose and use of
+
“On”
30°C
“Off”
“On”
“Off”
“On”
“Off”
40°C
30°C
30°C
Q
2
40°C
30°C
100
100
Q
2
H
2
Q
2
H
2
Q
2
80
80
60
60
40
40
20
20
0
0
02 46 8
Time
1/2
(h
1/2
)
10
12
0
2
4
6 8
Time
1/2
(h
1/2
)
10
12
Figure 9.4
Release of glucose from liquid crystalline matrix prepared from phytant-
riol containing 3% vitamin E acetate. [Modifi ed from Fong et al. (2009).]
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