In Vivo and In Vitro Elution of Analgesics from Multilayered Poly(D,L)-lactide-co-glycolide Nanofibers Incorporated Ureteral Stents

Abstract

We develop novel analgesic-eluting nanofiber-incorporated ureteral stents that offer sustained release of lidocaine and ketorolac for local drug delivery. Lidocaine and poly(D,L)-lactide-co-glycolide (PLGA) were dissolved in hexafluoroisopropanol and were electrospun into nonwoven nanofibers onto the surface of ureteral stents. This was followed by electrospinning of another layer of PLGA nanofibers containing ketorolac. Electrospun drug-loaded nanofibers were then characterized using scanning electron microscopy, Fourier transform infrared spectroscopy, and water contact angle analysis. In addition, the elution behavior characteristics of the analgesics, both in vivo and in vitro, from the nanofiber-incorporated stents were evaluated. Experimental results indicate that the analgesic-eluting ureteral stents could liberate high strengths of analgesics in vitro and in vivo for at least 50 and 30 days, respectively. The analgesic-eluting nanofiber-incorporated ureteral stents are potentially applicable for alleviating the discomfort associated with stent implant.

Drug-delivering devices in the urinary tract: A systematic review

“…A total of 485 publications were screened for eligibility and 29 articles were eventually included in the systematic review (Figure 1). Table 2 [9][10][11][12][13][14][15][16][17], Tab le 3 [3,[18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36] and Table 4 [3,33] show a summary of the included studies. The available studies were published over a period of 18 years (2000-2019).…”

“… Pathology examination of ureter: same pathologist minimising possible bias. 21 day follow-up: Group 1: 5 completely occluded 2 partially stenosed Group 2: no occluded stent Pathology examination 21 days: Obstructed R-stents generated severe inflammation with metaplasia PTX-eluting MS generated a mild inflammatory response without hindering ureteric patency The difference in length of the two stent groups Lin et al ., 2018 [ 32 ] 5 New Zealand White rabbits Ureter 5 cm segment of the analgesic (KL and lidocaine)-eluting nanofibre-incorporated ureter stent was inserted. Urine and blood samples were collected 1, 3, 7, 14, 21, and 28 days.…”

“…Two of the clinical trials involved DCB, of which one studied the use of DCB in the urethra [3], while the other investigated their use in the ureter [33]. In all, 19 clinical studies focussed on DES/DCS, of which 12 were about the use of DES/DCS in the ureter [12,[18][19][20][21][22]24,28,29,31,32,34] and seven in the urethra [16,23,26,30,[35][36][37].…”

“…Ketorolac, which is a NSAID, was tested in four studies [10,21,29,32]. Barros et al [10] tested the release profile of ketolorac from two different types of biodegradable stents, in artificial urine.…”

“…Overall, most of the drug was released within 30 days and the highest levels of the drug were found in the ureteric and bladder tissues in the stented groups in a dose-dependent fashion. Lin et al [32] studied the delivery of lidocain and ketorolac of a DES/DCS in vitro and in vivo in rabbit models. They showed that the DES/DCS was able to obtain high doses of analgesic for at least 50 days in vitro and 30 days in vivo.…”