Glucosomes: Glycosylated Vesicle‐in‐Vesicle Aggregates in Water from pH‐Responsive Microbial Glycolipid

Vesicle‐in‐vesicle self‐assembled containers, or vesosomes, are promising alternatives to liposomes because of their possible hierarchical encapsulation and high stability. We report herein the first example of sugar‐based vesicles‐in‐vesicles, which we baptize glucosomes. These were prepared by using a natural microbial glycolipid (branched C22 sophorolipid) extracted from the culture medium of the yeast Pseudohyphozyma bogoriensis. Glucosomes spontaneously formed in water between pH 6 and pH 4 at room temperature, without the requirement of any additive. By means of pH‐resolved in situ small angle X‐ray scattering, we provided direct evidence for the vesicle‐formation mechanism. Statistical treatment of the vesicle radii distribution measured by cryo‐tansmission electron microscopy by using a derived form of the Helfrich bending free‐energy expression provided an order of magnitude for the effective bending constant (the sum of the curvature and the saddle‐splay moduli) of the lipid membrane to K=(0.4±0.1) k (B) T. This value is in agreement with the bending constant measured for hydrocarbon‐based vesicles membranes.