| Summary: | Fibrosis-induced ureteric stricture is the narrowing of the ureter lumen that is caused by the formation of excessive collagen largely due to iatrogenic injuries. Stricture can result in severe consequences, such as hydronephrosis, renal failure, pain and even death. The current standard of care involving full thickness incision and post-operative stenting does not always produce successful outcome and recurrent stricture can occur, with prevalence rate up to 11%. Although drug therapy is an interesting and unexplored area in urology that could potentially offer a more viable treatment option, there are several challenges and stumbling blocks to overcome. Firstly, the urothelium has a barrier membrane with extremely high drug impermeability. Secondly, drug delivered in ureteric tract could be washed away easily by the urine flow. Thirdly, drug delivered by the current catheterization method can only be performed in the retrograde fashion which could only target bladder and distal ureter. Therefore, we proposed for the use of bilayer swellable drug-eluting ureteric stent. The coatings comprise of two layers: the first layer is an antiproliferative drug encapsulated in polymer and the second layer is a hydrogel which expands when it absorbs urine. This would allow for the sustained release of the drug to treat the chronic condition and the co-aptation of the expanded hydrogel with the diseased area of the ureter for the enhancement of drug transport into the highly impermeable urothelium to achieve the desired localized therapeutic effect.
The bilayer swellable drug eluting stent is fabricated by first spraycoating an antiproliferative drug, mitomycin C (MMC) encapsulated in a hydrophobic polymer, poly-L-lactide-co-caprolactone (PLC) onto the stent, followed by surface plasma treatment before coating a hydrogel, polyethylene glycol diacrylate (PEGDA) onto the polymer, via photo-crosslinking.
The effect of different plasma treatment times on interfacial adhesion between the hydrogel and drug-carrying polymer were studied. Four separate characterization techniques, namely static water contact angles, shear adhesion pull-off test, observation of hydrogel delamination for samples placed in static condition over 4 weeks, and atomic force microscopy (AFM) were carried out. It was found out that
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plasma duration (100W, 5 min) was effective in ensuring that the hydrogel stayed adhered on the stent for the 4 weeks period, and that this was facilitated by the increase in both surface hydrophilicity and surface roughness induced by the plasma treatment.
The drug release and transport was next conducted in a simulated ureteric tract system under dynamic fluid flow condition, in which it was found that there was significantly greater amount of drug released and transported intro explanted porcine ureters for samples with hydrogel compared to samples without. This could be explained by the high equilibrium water content of the hydrogel at above 90%. Moreover, the release follows a first order release kinetic in which the drugs are released from the polymer matrix via diffusion.
Therefore, based on these preliminary studies, we have established that the bilayer swellable drug eluting ureteric stent is feasible in sustaining and enhancing the localized delivery of the drugs into the targeted diseased area of the ureteric region to treat and manage stricture and its recurrence.
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