New delivery methods to get the best from novel medical compounds
Cancer tumours are notoriously hard to target with accurate drug delivery techniques. Other conditions also require compounds to arrive at precise locations with predictable release spans that allow medicines to be delivered over specific periods of time. The range of drugs being developed is growing but if we can’t get them to the right place at the right time then how can their therapeutic potential be harnessed? HYMADE, undertaken with the support of the Marie Curie programme, set out to explore the combination of heterogeneous materials of very different natures, (inorganic, organic and biological), to produce drug delivery vehicles with tailored properties. The ultimate goal of the HYMADE project was the development of capsules, and engineered colloidal particles, for drug delivery, which lead researcher Dr Sergio Moya is proud to confirm they managed to do. “We mainly worked with mesoporous colloids, highly porous materials with pores in the nanometre range that can be filled with drugs,” he explains. He focused on what is known as ‘the layer-by-layer’ technique, which is a simple technique for the self-assembly and engineering of colloids. The approach can also be used to encapsulate large therapeutics, such as antibodies and siRNAs, and virus-like particles called virosomes. Virosomes provide recognition properties and, by emulating the entry of virus in cells, facilitate the uptake of the particles or capsules. “Each of the elements used in the construction of the hybrid materials brings specific advantages and properties: the mesoporous colloids offer a way to encapsulate small molecules; the layer-by-layer technique provides a means to entrap larger molecules.” But arriving at these findings was a long road. The researchers undertook physico-chemical studies to understand the interaction among the different components of the hybrid materials, and how the properties of the hybrid materials can be fine-tuned. They also conducted transport studies to look into the release of encapsulated drugs in the hybrid materials, which are fundamental for their applications. Dr Moya explains: “We used a battery of techniques to trace the fate of the hybrid materials in vitro and in vivo. This is a very complex task, though very interesting. We aimed to follow the transformation of the hybrid materials in biological matrixes, their aggregation, degradation, and how the materials release encapsulated drugs inside cells or in vivo.” To do so the project used techniques such as confocal scanning laser microscopy, flow cytometry, confocal raman microscopy for cell work; and positron emission tomography and single photon emission computed tomography for in vivo work. “These last techniques required the labelling of the hybrid materials with radioisotopes. Through measuring the activity inside animal models, we were able to quantify the amount of hybrid materials per organ, and how these change with time following intravenous administration,” says Dr Moya. The extensive research undertaken by the project was the result of a network of researchers collaborating across Europe and beyond. “I am Argentinian, and the project involved a great deal of exchanges with Argentina, which has been very positive for the scientific development of the people who came from my country to Europe. I am proud of that,” he adds.
Keywords
HYMADE, hybrid materials, drug delivery, mesoporous colloids, biopharmaceutical, antibodies, siRNAs, virosomes