Stealth liposomes have been fundamentally explored for a number of decades and are now proving successful as components in the formulation of pharmaceutical products where they serve as the carrier substituent. They owe their applicability to a combination of structural characteristics that include their size (~100-nm diameter), large carrying capacity (~75 vol% hollow), colloidal stability (sterically-stabilized by poly[ethylene glycol] (PEG) on exterior surface), and biocompatibility/stealthiness (also derived from exposed PEG chains). The primary method of attaching PEG to liposomes is through the addition of a minority amount of lipid-capped PEG molecules into liposome formulations. Many studies have considered such stealth liposomes and structurally their focus has been on the impact of lipid-capped PEG fraction and PEG chain length. Here, we consider a unique aspect of the incorporating molecules’ architecture: the number of hydrophobic, bilayer-inserting units attached to each molecule. This is accomplished by studying a series of diblock copolymers wherein one block is PEG and the other is poly[cholesteryl 2-oxo-1,3,6-dioxazocane-6-carboxylate], which contains cholesteryl pendant groups that vary in quantity from one to five. We begin by probing the interaction of each copolymer with liposomes using isothermal titration calorimetry and by monitoring shelf-life stability via dynamic light scattering. Next, the structural details of the hybrid stealth liposomes are presented using both small angle neutron scattering and cryo-transmission electron microscopy. The combined interpretations from all experiments provide a critical value for the number of cholesteryl groups per molecule below which molecules serve their intended purpose and above which they do not. Ultimately, the ability to tune the number of bilayer-bound sites per molecule should lead to many additional studies, both fundamental and applied, on hybrid stealth liposomes.

Hybrid stealth liposomes via incorporation of cholesterol-functionalized diblock copolymers

253rd National Meeting (2017)

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