Transfersome

Transfersome is a term registered as a trademark by the German company IDEA AG, and used by them to refer to their proprietary drug delivery technology. Active components of living cells - the cellular machinery - tend to have names ending in "some", hence the obviously derived name for a sub-cellular transfer system. A Transfersome is an artificial vesicle designed to be like a cell vesicle, and used to deliver drugs or genetic material into a cell. Its bounding membrane is more flexible than that of a liposome, allowing it to deform and pass through openings in a barrier, such as the skin, whose diameters are much smaller than the average vesicle size.

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A Transfersome is an at least bi-component, most often vesicular, aggregate. The main functional characteristic of the aggregate is the extreme flexibility and permeability of its bilayer-like membrane coating. Its basis is the interdependency of local membrane shape and composition, which makes the bilayer self-regulating and self-optimising. The bilayer is thus capable of stress adaptation, via local and reversible bilayer component demixing. All this makes a Transfersome into a device suitable for non-invasive and targeted drug delivery, for example across intact skin.

Another beneficial consequence of high bilayer flexibility is the increased Transfersome affinity to bind and retain water. Ultradeformable Transfersome vesicles put in a dry environment therefore seek to find water richer region. This forces Transfersome vesicles applied on open skin to penetrate the skin barrier in a search for adequate hydration. The resulting vesicle migration is a consequence of continuous bilayer adaptation and deformation, but must not compromise unacceptably either the vesicle integrity or the protective skin barrier properties in real-life applications.

A basic Transfersome is composed of one natural amphiphat (such as phosphatidylcholine) that tends to self-aggregate into vesicles. The latter are then supplemented by at least one bilayer softener (e.g. a biocompatible surfactant). The vesicle-like Transfersome thus normally possesses an aqueous core surrounded by a complex, very fluid and adaptable lipid bilayer. In its basic organization broadly similar to a simple lipid vesicle (a so-called liposome), a Transfersome differs from the latter by its more flexible and permeable, "softened" bilayer membrane. A Transfersome vesicle can consequently change shape readily and easily by adjusting relative concentration of its two components in the bilayer to the local stress experienced by the complex bilayer. This can be observed indirectly by studying stress- or deformation-dependent vesicle bilayer elasticity or permeability. In a single experiment, the same goal can be achieved by determining the pressure dependency of Transfersome suspension-flux through a nano-porous filter (with the pores considerably smaller than the average vesicle size). The rate of resulting transport must grow with driving force (head pressure) non-linearly (often sigmoidally) until maximum flow is reached. For an ideal Transfersome, experiencing no friction in pores, the maximum flow is equivalent to the flux of the suspending liquid measured with a similar trans-filter pressure, and the minimum pressure required to attain good transport is a measure of bilayer flexibility. The observed functional dependency of suspension flux versus pressure can therefore be used to derive bilayer elasticity and flexibility, as well as permeability, based on theoretical description of the underlying enforced transport, viewed as an activated transport process.

References

• G. Gompper, D.M. Kroll (October 1995). "Driven transport of fluid vesicles through narrow pores". Physical Review E 52 (4): 4198–4208. doi:10.1103/PhysRevE.52.4198.
• G. Cevc, A. Schätzlein, H. Richardsen (2002-08-19). "Ultradeformable Lipid Vesicles can Penetrate the Skin and other Semi-Permeable Barriers Intact. Evidence from Double Label CLSM Experiments and Direct Size Measurements". Biochim. Biophys. Acta 1564: 21–30. PMID 12100992.
• G. Cevc, A. Schätzlein, H. Richardsen, U. Vierl (2003). "Overcoming semi-permeable barriers, such as the skin, with ultradeformable mixed lipid vesicles, Transfersomes, liposomes or mixed lipid micelles". Langmuir 19 (26): 10753–10763. doi:10.1021/la026585n.
• G. Cevc (2004). "Lipid vesicles and other colloids as drug carriers on the skin". Advanced Drug Delivery Reviews 56 (5): 675–711. PMID 15019752.

Further reading

• Science. IDEA AG. — IDEA's own detailed explanation of what Transfersomes are and what they do.
• What is the difference between liposomes and Transfersomes?. Scientific FAQ. IDEA AG.
• Medical trial that started in 2005