I started my internship a couple of days ago and I am very excited for my project.
Initially I was told I would be working on antibiotic delivery to wounds through an infinity-based system which I wrote about earlier but when I received my project description I realized I was working on a different area. Same concepts, but different application. My project will develop a delivery system for Paclitaxel utilizing Cyclodextrins through a bare metal stent, which will be functional under 600ml/min flow in an AV fistula.
When an AV fistula fails it is because of neointimal hyperplasia due to high stresses which leads to stenosis. The solution to this is angioplasty which is done through a drug-eluting stent, in this case Paclitaxel, an antiproliferation agent sold under the brand name Taxol, a common chemotherapeutic drug.
In plain language:
In patients with a high risk of kidney failure hemodialysis is the solution (pumping blood out of the body through an apparatus that removes toxin - a.k.a fake kidney). The best mechanism for dialysis is through an arteriovenous fistula. A fistula involves a surgical procedure of tying a vein directly to an artery, and skipping the arterioles, capillaries and venules that are in between. Blood in the artery flows with a high pressure whereas in the vein it has a low pressure. This difference creates unbearable shear stresses in the vein portion and the hope is the fistula will mature to sustain these stresses. In a lot of cases however the stress results in a series of events that ultimately cause more cell reproduction (neointimal hperplasia) in the region which leads to the narrowing of the vessel (stenosis) so it can no longer be used for hemodialisys.
The solution to stop the narrowing is to insert a metal stent (a tube to keep the vessel open). This however does not fix the cause of the problem (the increase in cell production) so it is not entirely efficient. But if the stent is coated with a antiproliferating agent (a drug to stop cell growth) then its release would stop cell growth and prevent the narrowing of the vessel.
Paclitaxol is one of these antiproliferating agents (a.k.a chemotherapeutic drug). But the problem with it is that it is very insoluble in aquaeous solutions. In order to overcome this issue one method is to use Cyclodextrins (CDs) - sugar molecules that are naturally a product of bacteria digesting cellulose. Fun fact - Febreeze uses them in their air-refreshing products. CDs have a teroid geometry with a very hydrophobic internal part which can host hydrophobic drugs like Paclitaxel and a very hydrophillic outside which helps dissolve the drug in aquaeous solutions.
So essentially what I'll be working on is getting the drug inside CDs in the right concentration for an AV fistula and getting it to dissolve for as long as possible in a linear fashion. The problem is Paclitaxel has always been used systemically not locally, so I'll have to figure out things from scratch instead of reading the literature.
Happy bioegineering,
A.M.D
