Biophysical Society Thematic Meeting | Ascona, Switzerland

Liposomes, Exosomes, and Virosomes: From Modeling Complex Membrane Processes to Medical Diagnostics and Drug Delivery

Friday Speaker Abstracts

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.

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