Synergy of Hydeal-D® and Hyaluronic Acid for Protecting and Restoring Urothelium: In Vitro Characterization.

Marco Ruggeri,Dalila Miele,Alba Di Lucia,Susi Panfilo,Carlo Barbera,Giuseppina Sandri,Franca Ferrari,Matteo Soato,Silvia Rossi,Mauro Pavan,Devis Galesso

doi:10.3390/pharmaceutics13091450

Marco Ruggeri, Dalila Miele + Show 9 more

Open Access

https://doi.org/10.3390/pharmaceutics13091450

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Journal: Pharmaceutics	Publication Date: Sep 11, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: University of Pavia, Fidia Farmaceutici (Italy)

Abstract

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction due to an inflammatory condition, characterized by bladder pain and urinary frequency. Currently, no gold standard therapy is available since IC does not respond to conventional ones. Given these premises, the aim of this work was the in vitro characterization of biological properties (mucoadhesion and anti-inflammatory activity) of a commercial product (HydealCyst–HydC) based on hyaluronic acid (HA) and the benzyl ester of HA (Hydeal-D®) intended for bladder instillation to restore and/or protect the urothelial layer of glycosamino glycans (GAGs). The in vitro characterization demonstrated that an interaction product is formed between HA and Hydeal-D® that has a role in the rheological behavior and mucoadhesive properties. HA was identified as a key component to form the mucoadhesive joint, while the interaction of HA with Hydeal-D® improved polysaccharide stability and prolonged the activity ex vivo. Moreover, HydC is cytocompatible with urothelial cells (HTB-4) and possesses an anti-inflammatory effect towards these cells by decreasing the secretion of IL-6 and IL-8, which were both increased in patients with IC, and by increasing the secretion of sulfated GAGs. These two findings, along with the resilience properties of the formulation due to mucoadhesion, suggest the active role of HydC in protecting and restoring urothelium homeostasis.

Highlights

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction of the pelvic walls, characterized by bladder pain and urinary frequency
The aim of this work was the characterization of HydealCyst (HydC), a commercial product based on Hyaluronic acid (HA) and Hydeal-D®, intended for bladder instillation and aimed at restoring and/or protecting the urothelial layer of glycosamino glycans (GAGs)
Considering the secreted regulatory and 6 report the concentrations of IL-6 and IL-8, respectively, by requirements for medical devices, the in vitro preliminary demonstration of safety tourothelial cells (HTB-4) after a 24-h stimulation with two different concentrations of TNFwards urothelial cells is mandatory at the preclinical level: these results indicate that the formulation is well tolerated by urothelial cells and is biocompatible

Summary

Introduction

Interstitial cystitis (IC) or painful bladder syndrome is a chronic dysfunction of the pelvic walls, characterized by bladder pain and urinary frequency It is an inflammatory condition affecting people of any age and gender, and it mostly occurs in women [1]. GAGs, in physiological conditions, coat the urothelium and play a crucial role in protecting the bladder and preventing the adhesion of pathogenic bacteria to the bladder [4,5,6]. Following damage to this protective layer, the infiltration of harmful urine components with inflammatory action into the underlying layers may occur, with consequent activation of mast cells [7].

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