The self-assembly of biomolecules occurs through weak noncovalent molecular interactions such as hydrogen bonds and hydrophobic interactions. Micelles with a hydrophobic core and hydrophilic exterior are easily created using amphiphilic block copolymers. But new opportunities in micellar design and functionality could be offered by generating block copolymer free micelles in which the hydrophobic and hydrophilic domains are generated instead through host-guest interaction.

Now researchers from Wuhan University in China1 describe simple methods to generate such micelles from alpha-cyclodextrin and the biodegradable polyester polycaprolactone, molecules already approved by the US Food and Drug Administration for use in the human body.

Fig. 1: Schematic of the synthesis of supramolecular micelles from alpha-cyclodextrin and poly(epsilong-caprolactone)

Cyclodextrins are cyclic oligosaccharides which form conical structures. When linear polycaprolactone in tetrahydrofuran was gently mixed with the solution of alpha-cyclodextrin in water, the linear molecules partially threaded through the conical structures. Removal of the tetrahydrofuran resulted in a second assembly in which the unthreaded portion of the polycaprolactone—which is hydrophobic—bundled into nanometre-scale spheres with the portion threaded through the oligosccharides forming a hydrophilic corona of width 6 nm which was exposed to the aqueous environment (Fig. 1). The researchers confirmed the structure of the micelles by using a competitive guest which they expected would expel the polycaprolatone from thealpha-cyclodextrin and destroy the micelles, this was confirmed by analysing the resulting structures with 1H NMR.

While this approach was somewhat successful, the researchers were disappointed with a yield of only 3 wt% of supramolecular micelles. To improve the yield, the researchers decided they needed to improve the solubility of the cyclodextrins by weakening their intermolecular hydrogen bonds to prevent their crystallization and precipitation. Two approaches were tried. First, urea was added into the synthesis pot. And second, the cyclodextrin was modified with maleic anhydride. Both approaches prevented crystallisation of the cyclodextrins and dramatically increased the yield of amorphous micelles.

Liu and colleagues investigated the practical utility of their micelles for drug delivery. Compared with traditional micelles, the researchers saw higher loading and more sustained release of an anti-inflammatory drug over 700 hours.