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Liposomes, Exosomes, and Virosomes: From Modeling Complex
Membrane Processes to Medical Diagnostics and Drug Delivery
Friday Speaker Abstracts
47
Dynamic Creation of Nanostructured Lipid Self-assembled Mesophases via Invertase
Digestion Triggers Controlled Release of Encapsulated Drug
Wye Khay Fong
1,2
, Francesco Ortelli
1
, Wenjie Sun
1
, Sánchez-Ferrer Antoni
1
, Ben Boyd
2
,
Raffaele Mezzenga
1
.
1
Monash University, Parkville, Victoria, Australia,
2
ETH Zürich, Zürich, Switzerland.
The development of enzymatically responsive matrices has been of recent interest in the drug
delivery field as it can take advantage of enzymes that are over-expressed in diseases such as
cancer in order to trigger the release of encapsulated molecules. These ‘smart’ materials have the
potential to provide early detection of disease and provide site selective drug release, thereby
minimising exposure of healthy tissues to toxic drug, whilst maximising drug effectiveness.
In this study, geometrically ordered lipid nanoparticles with internal bicontinuous cubic phase
structure were dynamically formed via enzymatic digestion with invertase. A simple liposome
forming lipid mixture containing a mixture of a non-digestible lipid (phytantriol) and a digestible
sugar ester (sucrose laurate) was transformed to the cubic phase via enzymatic hydrolysis of the
sugar head group. The digestion of the headgroup results in the exit of a monosaccharide from
the interface and consequently the alteration of the lipid packing in the liposomes, resulting in
crystallization of the cubic-phase internal nanostructure. Time-resolved small-angle X-ray
scattering (SAXS) revealed the kinetics of the order-to-order transition, with HPLC and an
enzymatic method used to quantify the digestion kinetics of the sugar ester.
Controlled release was then demonstrated with this invertase responsive matrix. A model dye,
fluorescein, was encapsulated into the vesicles and release was triggered upon digestion with
invertase. This designer approach to creating specialised drug delivery systems, whereby an
amphiphile susceptible to digestion by a specific enzyme results in a phase transition and
therefore drug release, presents a highly sought after enzymatic method for triggered release.