Charged vesicle suspensions have found an increased use in drug delivery, micro/nanoreactors, gene delivery, fabric enhancers and cosmetics. Microstructural transformations in cationic unilamellar vesicles are studied by the addition of crowding species to the vesicle solution to induce depletion interactions. We investigated the change in the morphology of cationic DOTAP-cholesterol unilamellar vesicles based on such mechanisms with a view to understanding the fundamentals of liposome structure in DNA plasmid encapsulation and gene delivery. Starting with model small molecule and polymer-based crowders, we show the generation of depletion attraction forces which act in conjunction with electrostatics and membrane elasticity to cause vesicle deflation and the formation of stomatocyte intermediate structures. The self-fusion of the stomatocytes results in the formation of bilamellar vesicles, while the wrapping of stomatocyte on the intact vesicles leads to the formation of multilamellar vesicles. The transitions from unilamellar to bilamellar structures induced by different crowding species along with intermediate morphologies are illustrated using cryo-TEM and small angle neutron scattering (SANS) analysis. This crowding induced bilayer transformation can be helpful in designing drug and gene delivery systems.

Transition of unilamellar cationic liposomes to bilamellar structures through the depletion effect

255th National Meeting (2018)

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