Composition and Structure - Lipid Nanoparticles: Production, Characterization and Stability - page 12

disappearance with time thus creates an obvious issue to drug loading. This results
in drug expulsion during storage or burst release after administration. Another fac-
tor that influences the selection of an appropriate lipid is thus its tendency to form
perfect crystalline lattice structures or, at least, the rate at which metastable-to-
stable transitions take place. No definitive guidelines exist for the choice of lipids
based on these properties.
Generally, crystallisation in lipids with longer chains of fatty acids are slower
than those with shorter fatty acid chains (Wong et al. 2007 ). Wax-based lipid nano-
particles are physically more stable, however they exhibit significant drug expul-
sion due to their more crystalline nature (Jenning and Gohla 2000 ). To avoid such
problems with lipid crystallinity and polymorphism, a binary mixture of two spa-
tially different solid lipid matrices, i.e. a solid lipid and a liquid lipid (or oil) was
used to prepare lipid nanoparticle dispersions, now known as “nanostructured lipid
carriers (NLC)” (Jenning et al. 2000d ; Müller et al. 2002a ; Souto et al. 2004 ).
Cationic lipids utilised in lipid nanoparticle preparation have been reported for
use in gene delivery. The positive charge on the particle surface due to the use
of a cationic lipid may enhance transfection efficiencies. Two-tailed (or branched)
cationic lipids are preferred over one-tailed cationic lipids due to the cytotoxic-
ity of the latter (Tabatt et al. 2004a , b ). Examples of the lipids (including cationic
lipids) which have been used in the preparation of lipid nanoparticles, both SLNs
and NLCs, are listed in Table 2.1 .
2.1.2 Surfactants
Surfactants (also known as surface-active agents or emulsifiers) form the other
critical component of the lipid nanoparticle formulation. Surfactants are amphip-
athic molecules that possess a hydrophilic moiety (polar) and a lipophilic moiety
(non-polar), which together form the typical head and the tail of surfactants. At
low concentrations, surfactants adsorb onto the surface of a system or interface.
They reduce the surface or interfacial free energy and consequently reduce the sur-
face or interfacial tension between the two phases (Corrigan and Healy 2006 ).
The relative and effective proportions of these two moieties are reflected in
their hydrophilic lipophilic balance (HLB) value. Surfactants used in the prepara-
tion of lipid nanoparticle preparations play two quite distinct and important roles
• Surfactants disperse the lipid melt in the aqueous phase during the production
process
• Surfactants stabilize the lipid nanoparticles in dispersions after cooling
Surfactants can be broadly categorized into three classes based on their charge:
ionic, non-ionic and amphoteric. Table 2.2 lists a few surfactants from each class
used in the preparation and stabilization of lipid nanoparticles. In all cases, the
surfactants are surface tension lowering, which aids in the dispersion process
required to form the product (first role). Ionic surfactants are traditionally thought