Finding biocompatible carriers that can get drugs to their targets in the body involves significant challenges. Beyond practical concerns of manufacturing and loading these vehicles, the carriers must work effectively with the drug and be safe to consume. Vesicles, hollow capsules shaped like double-walled bubbles, are ideal candidates, as the body naturally produces similar structures to move chemicals from one place to another. Finding the right molecules to assemble into capsules, however, remains difficult.
Researchers from the University of Pennsylvania have now shown a new approach for making vesicles and fine-tuning their shapes. By starting with a protein that is found in sunflower seeds, they used genetic engineering to make a variety of protein molecules that assemble into vesicles and other useful structures.
The research was conducted by Daniel A. Hammer, Alfred G. and Meta A. Ennis Professor of Bioengineering, graduate student Kevin Vargo and research scientist Ranganath Parthasarathy of the Department of Chemical and Biomolecular Engineering in Penn’s School of Engineering and Applied Science.
Hammer's group worked for nearly a decade to find a protein that was biocompatible, could be produced through recombinant methods and, most important, could be induced to form vesicles.
'Recombinant methods mean we can make polymers that are all of a defined length and dictate the chemical composition at each location along that length,’ Daniel Hammer said: ‘You get the exact length and sequence every time.’
According to Hammer’s team, the hardest part of the research was confirming that these sequences did indeed fold into vesicles. This was only possible with specialized equipment. The imaging technique used is known as cyro-transmission electron microscopy, or cryoTEM.
As their protein is already routinely eaten, the researchers are confident that their oleosin vesicles will be of great interest in drug-delivery applications, particularly oral-drug delivery. Future work will entail adding genes for functional groups to allow the vesicles to target certain tissues, as well as determining whether the proteins can be induced to change shape once they reach their targets.
‘This research opens up the possibility of using switchable motifs to allow us to release high concentrations of drugs on different cues, such as a change in acidity,’ Hammer said. ‘Tumour microenvironments and the interior of tumours are known to be acidic, so a vesicle that falls apart in acidic environments would be extremely valuable.’
Their work was published in the Proceedings of the National Academy of Sciences. (PNAS 2012; published ahead of print July 2, 2012, doi:10.1073/pnas.1205426109)
