Polymer vesicles are assemblies of amphiphilic block copolymers—chemical compounds that both like (hydrophilic) and dislike (hydrophobic) water—formed by interactions between molecules and, in recent years, the structures have shown potential for various biological applications. The hydrophobic regions of their membranes, however, are such that the transport of hydrophilic molecules across them, whilst maintaining the vesicles’ structure, is often not possible.

Now, Hsin-Cheng Chiu and co-workers at the National Chung Hsing University, Taiwan1 have synthesised polymer vesicles that allow hydrophilic molecules to pass through channels created in their membrane when the external pH is within a certain range. The vesicles—made from copolymers of acrylic acid and distearin acyrlate—have membranes formed from discontinuous lipid bilayers: The gaps between these bilayer sections contain un-ionized acrylic acid functions and, as the external pH increases, the ionization in the acrylic acid residues increases to a point where the channel becomes permeable to hydrophilic molecules.

The researchers demonstrated the reversibility of the process using the fluorescent probe molecule, calcein. At low pH, the molecule cannot be transported across the membrane and remains in the surrounding solution, but at a higher pH the molecule ventures into the vesicle. If the pH is lowered again, calcein becomes trapped in the confines of the vesicle. The same transport phenomenon is seen for larger molecules, such as haemoglobin.

Fig. 1: An imaging using laser scanning confocal microscopy techniques of a polymer multi-vesicle assembly in which four smaller vesicles are contained within a larger one.

Another important design feature for these polymer vesicles is the use of a two-step emulsion method to make multi-vesicle assemblies that comprise several smaller vesicles within the aqueous environment of a larger vesicle (Fig. 1).

Chiu envisages these multi-component assemblies being used as drug delivery vehicles that can load different therapeutic agents individually into the smaller vesicles and these agents are only mixed on release.

The Taiwanese group are hoping to investigate many structural and functional aspects of the multi-vesicle assemblies in the future. “We will be focusing on the precise control of the multi-vesicle morphology, such as the number of small vesicles in the larger ones, the channel size and the adjustment of the pH ranges that trigger the channels’ opening and closing,” says Chiu.