Chemistry Reference
In-Depth Information
8.5 “ON DEMAND” LYOTROPIC LIQUID CRYSTAL-BASED
DRUG DELIVERY SYSTEMS
Based on the principle that the H
II
phases released model hydrophilic and
hydrophobic drugs more slowly than the GMO cubic phase matrix, Fong et al.
(2009) designed phytantriol and GMO-based bicontinuous cubic (Q
2
) and H
II
nanostructures, designed to allow change to the nanostructure in response to
an external change in temperature, with an intention of eventual control of
drug release rates in vivo. Using glucose as a model hydrophilic drug, drug
diffusion was shown to be reversible on switching between the H
II
(very low
release) and Q
2
nanostructures (high release), at temperatures above and
below the physiological temperature, respectively (Fig. 8.15).
However, the matrix used by Fong et al. (2009) required the inclusion of a
modifi er (vitamin E acetate) to reduce the transition temperature close to
physiological temperature for in vivo application, thereby enabling control
over the structure by application of, for example, a heat pack to the skin
surface after subcutaneous administration. This is a major limitation as there
is no specifi city in the heat source; hence, exposure to extremes of temperature
may unintentionally induce drug release. Consequently, an alternative means
to induce the phase transition was necessary that did not require direct heating
and did not require a reduction in the temperature at which the transition
occurs, ideally occurring at the inherent transition temperature without addi-
tive (approximately 55°C for phytantriol), removing the potential for acciden-
tal activation.
30°C
40°C
30°C
100
Q
2
H
2
Q
2
80
60
40
20
0
0
2
4
6
Time
1/2
(h
1/2
)
8
10
12
Figure 8.15
Dynamic release profi les for glucose into phosphate-buffered saline from
3% vitamin E acetate with changing temperature, plotted against square
root of time. Temperature was switched from 30°C
phytantriol
+
30 ° C at the times indi-
cated by the dashed lines in order to form the phase transition cubic
→
40 ° C
→
→
hexago-
nal
→
cubic (Fong et al., 2010 ).
Search WWH ::
Custom Search