Stimuli-Responsive Liposomal Drug Delivery Platforms for Controlled Release

Liposomes are effective drug delivery nanocarriers due to their unique bilayer structure and versatile nature in encapsulating both hydrophilic and hydrophobic drugs within the hydrophobic bilayer and aqueous core, respectively. To control the time and location of cargo release, different triggered release strategies have been developed to minimize off-target effect as well as increase the drug potency. Commonly explored stimuli include internal stimuli (i.e. pH) or external stimuli (i.e. light). To expand the toolbox, here, we present novel strategies for targeting a variety of stimuli, all of which are proven to be upregulated in certain diseased cells and are closely related to numerous pathological conditions. To do so, lipids are designed to undergo chemical or conformational changes upon coming in contact with target stimuli. Such structural changes are expected to disrupt the membrane integrity and cause the release of encapsulated cargo when these lipids are incorporated within the membrane bilayer. For each case, the design and synthesis of the desired responsive lipids will be discussed. Fluorescence-based release assays to evaluate release properties utilizing both hydrophilic and hydrophobic dyes, as well as dynamic light scattering (DLS) analysis and scanning transition electron microscopy (STEM) techniques to probe the membrane property change before and after triggered release will also be presented.