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consistent with the progression of the lipid structure toward a new phase from
the incorporation of d-DOPC in the GMO domains. This demonstrates that a
phase transformation of LCNP can occur when an interfacial interaction alters
the composition of the crystalline particles.
Phase transformation can also be triggered by an external stimulus such as
a change in osmotic gradient. Studies have shown that GMO lipid membrane
in a polymer scaffold is responsive (Aberg et al., 2008). When the osmotic
gradient is above a critical transition point, a cubic to lamellar phase is induced
at the surface of the membrane. This phase transformation drastically reduces
the permeability and changes the diffusive transport behavior. Before the
phase transformation, small compounds are rather permeable in the bicon-
tinuous cubic phase. After the transformation, the lamellar phase reduces the
diffusion transport (Sparr et al., 2009). The similar nature of the responding
membrane is seen in skin, where gradients can alter the molecular structure
in the membrane and thereby regulate the transport across a barrier (Sparr
et al., 2009 ).
10.6.3
Effect of Including Guest Molecules
The internal phase of the dispersed LCNPs can be affected by the presence
of a steric stabilizer, by the addition of guest molecules, and may also be
changed upon interaction at the interface. A steric stabilizer is required for
the stable dispersion of the bulk crystalline phases; however, the nature and
quantity of the stabilizer may itself induce a change in the crystalline phases
in the dispersed particles (Boyd et al., 2009). The effect of stabilizer is specifi c
to the lipid-stabilizer combination. For example, the F-127 stabilizer can
change the GMO-based particle from the diamond bicontinuous cubic phase
(Pn3m) to the primitive bicontinuous cubic phase (Im3m) at high concentra-
tion but not with other lipids such as phytantriol or glyceryl monolinoleate
(Boyd et al., 2009).
Inclusion of guest molecules such as drugs and other additives can also
affect the internal crystalline structure of LCNP. Phase transformations have
been observed in the bulk crystalline phases and also in the internal structure
of the dispersed particles. For specifi c examples, see reviews by Drummond
and Fong (1999), Shah et al. (2001), and Boyd et al. (2009) for bulk gel phase
and dispersed particles, respectively. As a general rule, addition of hydrophobic
molecules encourages transformation from reversed cubic to reversed hexago-
nal phases, while the inclusion of hydrophilic molecules induces curvature
toward the lipid region and favors lamellar phases (Boyd et al., 2009; Shah
et al., 2001). For example, addition of vitamin E acetate to phytantriol (Dong
et al., 2006) and glyceryl trioleate to GMO (Mele et al., 2004) results in trans-
formations of cubic phase to hexagonal phase. This is in contrast to the
addition of charged membrane lipid, dipalmitoylphosphatidylserine (DPPS),
to phytantriol, which converts the cubic phase into the lamellar phase and
results in the increased presence of vesicles (Shen et al., 2010).
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