Stefaan De Smedt and Bruno De Geest of Ghent University, Belgium, weigh up the pros and cons of using polyelectrolyte capsules as drug delivery vehicles 

Pharmaceuticals and therapeutic molecules, such as proteins or peptides, often need suitable carriers to deliver them safely to target cells while protecting them from being broken down by extracellular enzymes. Developing microscopic vehicles for this purpose, which can release their payload on cue, is a major focus in the field of drug delivery. Over the years, a variety of micro- and nanocarriers have been developed, such as liposomes or block copolymer micelles.

More recently, a new type of capsule has emerged as a promising candidate for biomedical applications.  Polyelectrolyte capsules are made by layer-by-layer coating of a sacrificial template, which then decomposes. The layer-by-layer technique is based on the sequential adsorption of charged species, such as polymers, nanoparticles, or lipids onto an oppositely charged substrate. Multilayers based on, for example, hydrogen bonding or click-chemistry, have also been reported. 

Polyelectrolyte capsules can decompose and release their contents upon physical, chemical or biological triggers. In general, chemical triggers work by altering the electrostatic interactions between the successive polyelectrolyte layers. For example, a simple way of decomposing polyelectrolyte multilayers is by changing the pH of the surrounding environment.  This causes the charge density of one of the polyelectrolytes to change, leading to repulsion between like charged polyelectrolytes. This in turn causes the capsules to dissolve. 

Increasing the ionic strength of the environment can cause the polyelectrolyte shell to swell and eventually dissolve. This is due to ions shielding the electrostatic charges that hold the polyelectrolytes together.

Although the above approaches to drug release seem promising, the extreme pH and ionic strength conditions that would be needed to dissolve the capsules are not compatible with physiological conditions. 

A physical trigger, such as an infrared laser, can be used on polyelectrolyte capsules that have been loaded with metal nanoparticles. Infrared irradiation heats up the nanoparticles, causing them to vibrate. This creates holes in the polyelectrolyte shell, allowing the encapsulated material to escape. This method can even result in complete explosion of the capsules. This kind of release mechanism might be useful for drug delivery activated through the skin, because infrared radiation can penetrate a few millimetres into the tissue.

Polyelectrolyte capsules can also be opened by biochemical triggers. When using bio-polyelectrolytes, such as polypeptides or polysaccharides, the capsules are prone to enzymatic degradation. Such capsules can also be internalised and broken down by cells. These capsules could be used to deliver antigens for vaccination purposes, or genetic material such as DNA. 

In the examples above, drug release is activated by external triggers, but drug release from polyelectrolyte capsules can also be governed by internal mechanisms. Self-exploding microcapsules can be made from a degradable microgel core, surrounded by a polyelectrolyte membrane. When the microgel core degrades, the swelling pressure increases and eventually ruptures the surrounding polyelectrolyte membrane. By tailoring the degradation rate of the microgel core it should be possible to precisely tailor the capsule's explosion time. 

 

This capsule will self-destruct in one minute: the microgel core (green) expands, causing the polyelectrolyte shell (red) to rupture

 

The major advantage of polyelectrolyte capsules is their multifunctionality - their composition can easily be optimised without complicated chemistry or hazardous procedures. However, the fabrication of polyelectrolyte capsules still remains rather laborious, and so far there are no polyelectrolyte capsules ready for clinical testing. Scientists from different fields must combine forces to work on scaling-up the production process of polyelectrolyte capsules, improving their stability and exploring their toxicological and immunological properties.

Read Stefaan De Smedt's review on 'Release mechanisms for polyelectrolyte capsules' in issue 4, 2007 of Chem. Soc. Rev.