Liposomes (vesicles) are spherical nanocontainers formed by the self-assembly of phospholipids in water. They are widely used as nanocarriers for drug-delivery. Payloads encapsulated in the aqueous core of liposomes can be released slowly by passive diffusion through the lipid bilayer. Alternately, the payload can be released en masse if the liposomes are converted into micelles (note that micelles, unlike liposomes, have a hydrophobic core). Recently, there has been much interest in devising liposomes that can be induced to transform into micelles by external stimuli such as temperature, pH, or light. Such responsive systems have been investigated in the context of formulations for drug-delivery. Many of these responsive liposomes are based on specially synthesized lipids or on mixtures of lipids with single-tailed surfactants.<br/> <br/>Here, we demonstrate that a thermally induced transition of liposomes into micelles can be realized in a very simple system that uses only a single phospholipid. We work with soy lecithin, a lipid with a phosphatidyl choline headgroup that is inexpensive and commercially available. The responsive system is obtained by forming liposomes of the lecithin in mixtures of water and a co-solvent such as ethanol. Liposomal samples at low ethanol fractions remain unchanged as a function of temperature. However, when the ethanol fraction crosses a threshold value, the samples undergo a transition from a turbid dispersion of liposomes (~ 100 nm diameter) at room temperature to a clear solution of spherical micelles (~ 5 nm diameter) above a critical temperature. The critical temperature can be varied by changing the water:ethanol ratio. Small-angle neutron scattering (SANS) and cryo-electron microscopy (cryo-EM) are used to confirm the above microstructural transition. To understand the fundamental origins of the above transition, we have investigated the temperature-dependent phase-behavior of lecithin/water/alcohol mixtures over a wide range of compositions. The discovery of thermal transitions in these simple liposomal systems could prove useful in both medical and cosmetic formulations.

Simple class of responsive liposomes that transform into micelles upon heating

2019 Spring National Meeting

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