Tethering is a patented mechanism to facilitate the delivery of an Agent of Interest (AOI) to the relevant tissue in a targeted way. Tethersomes can travel across the skin barrier in a similar way to Sequessome vesicles and Transfersomes. The difference between a Tethersome and a Sequessome vesicle or Transfersome is that a Tethersome has an AOI attached to its outer surface. This means that the AOI is presented to the target tissue where it can have its desired effect.
A Tethersome is made by covalently bonding the AOI to the head group of a fatty acid chain. The fatty acid chain is then introduced into the wall of a Sequessome vesicle (or liposome if administered IV) where it has a strong affinity for the other fatty acids in the vesicle wall. This affinity is not a covalent bond but a like for like attraction caused by the complimentary polarity of the adjacent fatty acid molecules.
The nature of the covalent bond used to tether the AOI determines whether and when the AOI is released. For instance, if an ester bond is used the AOI will be cleaved off as soon as the tethersome comes into contact with esterases (an enzyme that preferentially cleaves/chops up esters). If a different bond is used a different enzyme can release the AOI. In some cases the AOI will not be released as the covalent bond chosen is highly robust.
The longer the AOI is attached to the tethersome the longer it will remain in the target tissue as the size of the attached tethersome means it cannot be cleared by capillaries or by the microvasculature.
The benefit of this mechanism, which relies on the strength of the non-covalent bonding within the vesicle wall to withstand the drag effect of pulling the AOI through the skin and other tissue, is that specific amounts of AOI can be delivered in a targeted local way, avoiding side effects, unnecessary levels of systemic dosing, and delivering more AOI to the target tissue. This method is particularly relevant for AOIs that are lipophilic and would prefer to remain in the lipid membrane if introduced by use of a Transfersome.