Scientists in Australia and Germany have used living cells as 'factories' to encapsulate particles such as drugs in biological membranes. The system could be used in the future as a biocompatible drug-delivery vehicle that could evade the body's immune and excretory systems, the scientists suggest.
Dayang Wang of the University of South Australia and Adelaide, and colleagues showed that certain hydrophobic molecules, including drugs and dyes, can diffuse across the membranes of cultured human or mouse cells. These molecules are then acted upon by enzymes in the cell to create the active hydrophilic product, which because of its water loving properties can remain in the cell's cytoplasm.
The capsules are released through protein channels in the cell membrane
© Nano Letters
The next stage is to parcel up these particles within much smaller membrane capsules. The researchers did this by exposing the cells a substance called cytochalasin B, which disrupts the internal scaffolding of the cell, its cytoskeleton. When the cells are then shaken, the membrane breaks up into many smaller hollow spheres, typically 1-2 micrometres in diameter, containing the introduced molecule.
The team showed that the membrane proteins, including receptors and ion channels, remain in the membranes of the smaller vesicles, and that these can, in certain circumstances, be stimulated by an appropriate biochemical cue to release the contents of the vesicle. The team showed that the vesicles can largely evade the attention of macrophages, cells which circulate in the blood and mop up foreign particles.
'We wish that in the future one could use cells directly from patients to encapsulate drugs, magnetic nanoparticles and other biological labels and inject these loaded capsules back into the patients,' says Wang. 'Since the capsules are derived from patients, there should be no clearance by macrophages or the renal system.'
Martin Garnett, a drug delivery expert from the University of Nottingham in the UK, says that the work is 'interesting in terms of how drugs can be loaded into containers produced from cell membranes and cytoplasm'. The fact that the capsules are not readily taken up by macrophages is also significant, he says. However, Garnett adds: 'As with other drug delivery systems the question of payload will have to be resolved. In the current paper the loading of drugs is dependent on having a hydrophobic drug which can be metabolised into a hydrophilic drug to retain it, and this may be applicable to only a small number of drugs.'
Simon Hadlington
RSC
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