Development and Characterization of a Hydrogel Containing Silver Sulfadiazine for Antimicrobial Topical Applications. Part II: Stability, Cytotoxicity and Silver Release Patterns

Lilian Vieira Vaz,Marta Maria Duarte Carvalho Vila,Valquíria Miwa Hanai Yoshida,Victor Manuel Balcão,José Martins Oliveira Jr,Angela Jozala,Matthieu Tubino

doi:10.1590/s2175-97902022e18688

Abstract

Hydrogels are interesting for use in the treatment of topical wounds due to their virtually zero toxicity, and capacity for extended release of pharmaceuticals. Silver sulfadiazine (SSDZ) is the drug of choice in the treatment of skin burns. The aim of the study was to determine cytotoxicity, antimicrobial activity and stability of a PVA hydrogel with integrated silver sulfadiazine. SSDZ-hydrogels were prepared using 10% (w/w) PVA (either 89% or 99% hydrolyzed) and 1% (w/w) silver sulfadiazine. Cellular viability was assessed via MTS assays, antimicrobial activity via disk-diffusion and accelerated stability tests were carried out with analysis at 0, 30, 60, 90 and 180 days of storage at 40 ± 2 °C and a relative humidity of 75 ± 5%. The parameters evaluated included organoleptic characteristics, moisture, swelling ability, mechanical strength, FTIR, XRD, TGA and DSC, and silver release patterns via XRD and potentiometry. Cell viability tests indicated some cytotoxicity, although within acceptable levels. After 90 days of storage, SSDZ hydrogel samples exhibited a brown coloration, probably due to the formation of Ag or Ag2O nanoparticles. The SSDZ-loaded hydrogels suffered visual and physical changes; however, these changes did not compromise its use as occlusive wound dressings or its antimicrobial properties.

Highlights

Biotechnology has contributed greatly to the development of numerous sectors, with health being one of the fields in which this technology has had the most impact
Regarding pharmaceutical products indicated for use in the treatment of skin burn injuries, there is a consensus on the use of silver sulfadiazine (SSDZ) at 1% (w/w) (International Consensus, 2012; Farjado et al, 2013; Serra et al, 2015)
Hepatic toxicity, renal toxicity, and leukopenia have been reported in large wound treatments using topical application of silver sulfadiazine, but with use justified by their antimicrobial efficacy (Shahzad, Ahmed, 2013)

Summary

Introduction

Biotechnology has contributed greatly to the development of numerous sectors, with health being one of the fields in which this technology has had the most impact. Given the advantages observed in hydrogels for the treatment of wounds, especially skin burns, many researchers have developed and characterized hydrogels with silver compounds (Farjado et al, 2013; Serra et al, 2015). For the success of a product and its industrial production, it is necessary to evaluate its lifetime of the product, in order to ensure its effectiveness and maintenance of its physical properties over time. Considering these facts, the main goal of the research effort was to evaluate a PVA hydrogel incorporating SSDZ in relation to its cytotoxicity, antimicrobial activity and stability during a storage timeframe of 180 days. The SSDZ-loaded hydrogel formulation was characterized physicochemically, encompassing surface morphology via Field Emission Scanning Electron Microscopy (FESEM), thermal analyses by Differential Scanning Calorimetry (DSC), infrared spectrophotometry with Fourier transform (FTIR), and X-ray diffraction analyses (XRD)

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Results

Conclusion