A pH responsive film that releases drugs to kill cancer cells could find applications from implant coatings to drug delivery systems, say scientists in the US and Korea.

Paula Hammond from Massachusetts Institute of Technology, Cambridge, and colleagues created the film by trapping polymeric spheres in a multilayered surface. To make the spheres they attached a hydrophobic chemotherapeutic agent - doxorubicin - to a biocompatible polymer using a labile, pH-responsive linker. On adding a buffer, the drug-loaded polymer forms a suspension of spherical hydrophobic micelles in the aqueous liquid. The researchers then integrated the micelles into thin films using a layer-by-layer (LbL) deposition technique. 

Usually it is difficult to incorporate hydrophobic species into layers under physiological conditions (pH 7.4) due to their limited functionality. Hammond overcame this problem by creating a hydrogen-bonded system, using tannic acid, a compound found in tea. The acid forms hydrogen bonds with the polymeric micelles ensuring that the multilayer remains stable and intact under biological conditions. 

Drug-loaded micelles are trapped between layers of tannic acid to build the multilayer films

The pH-responsive linkers in the micelles can then be used to control doxorubicin's release from the film when it is required, by changing the pH conditions of the solution surrounding the film. Hammond's team was able to demonstrate this in tests with cancer cells and showed that the doxorubicin remained bioactive even after encapsulation in the film.

Frank Caruso, an expert in the field of LbL assembly for biomedical applications, based at the University of Melbourne, Australia, says that the strategy is an innovative approach to drug delivery. 'Such films are likely to serve as a platform technology to develop engineered thin films with potential in the delivery of therapeutics in biomedical applications,' he suggests.

Hammond says that future work could look at combining drug-loaded micelles that respond to different chemical or physical triggers, such as redox reactions or light. Hammond adds that their drug release system could be used as an ultrathin surface coating that she hopes 'will be of great interest for localised delivery of cancer therapeutics and vaccines.' To achieve this, she explains, a particular challenge will involve making all individual components of the LbL constructs fully biocompatible and non-toxic. 

Emma Shiells

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