Abstract

Conventional technologies for ureteral stent fabrication suffer from major inconveniences such as the development of encrustations and bacteria biofilm formation. These drawbacks typically lead to the failure of the device, significant patient discomfort and an additional surgery to remove and replace the stent in the worst cases. This work focuses on the preparation of a new nanocomposite material able to show drug elution properties, biodegradation and eventually potential antibacterial activity. Poly(2-hydroxyethyl methacrylate) or the crosslinked poly(2-hydroxyethyl methacrylate)-co-poly(acrylic acid) hydrogels were prepared by the radical polymerization method and combined with a biodegradable and antibacterial filling agent, i.e., flower-like Zinc Oxide (ZnO) micropowders obtained via the hydrothermal route. The physico-chemical analyses revealed the correct incorporation of ZnO within the hydrogel matrix and its highly mesoporous structure and surface area, ideal for drug incorporation. Two different anti-inflammatory drugs (Ibuprofen and Diclofenac) were loaded within each composite and the release profile was monitored up to two weeks in artificial urine (AU) and even at different pH values in AU to simulate pathological conditions. The addition of mesoporous ZnO micropowders to the hydrogel did not negatively affect the drug loading properties of the hydrogel and it was successfully allowed to mitigate undesirable burst-release effects. Furthermore, the sustained release of the drugs over time was observed at neutral pH, with kinetic constants (k) as low as 0.05 h−1. By exploiting the pH-tunable swelling properties of the hydrogel, an even more sustained release was achieved in acidic and alkaline conditions especially at short release times, with a further reduction of burst effects (k ≈ 0.01–0.02 h−1). The nanocomposite system herein proposed represents a new material formulation for preparing innovative drug eluting stents with intrinsic antibacterial properties.

Highlights

  • Nowadays, the use of ureteral stents is a conventional and routine practice

  • New composite materials based on the incorporation of mesoporous flower-like Zinc Oxide (ZnO)

  • Micropowders into polyHEMA and poly(HEMA-co-acrylic acid (AA)) hydrogels were investigated for drug eluting stents applications

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Summary

Introduction

The main limitations of current ureteral stents are (i) the encrustation of the system induced by the precipitation of inorganic salts from urine and (ii) the formation of bacteria biofilm, with consequent antibiotic resistance, persistence of the infections, morbidity, urinary retention, ureteral damage and in the worst cases pyelonephritis and sepsis [1,2]. All these drawbacks lead to significant patient discomfort (pain, urgency, frequency) and a second surgery to remove or replace the stent, even often supported by an alongside antibiotic, analgesic or other drug treatments [3]. These included the use of antimicrobial silver [6], hydrogels (like Hydromer® ) [7], heparin [8]

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