Influence of crosslinking degree on hyaluronan gel properties and in vitro cytotoxicity

Abstract

Trabajo presentado en la VII Jornada IN2UB, celebrada en Barcelona el 26 de enero de 2017.Hyaluronan (HA) is a natural polysaccharide widely distributed into the human body that can be used in biomedical and pharmaceutical applications [1]. As HA is degraded in vivo by hyaluronidase [2], the preparation of materials based on chemically crosslinked HA for drug delivery could represent a useful approach for increasing the in vivo resistance to degradation [3]. Hydrogels are crosslinked networks of hydrophilic polymers used as drug delivery systems via several administration routes [4,5]. The aim of this work was to study the crosslinking effect of HA hydrogels on drug release properties and in vitro cytotoxicity. HA hydrogels were prepared with different degrees of crosslinking using butanediol diglycidyl ether (BDDE) as a crosslinking agent. A lipophilic model drug, ketoprofen, and a hydrophilic model drug, theophylline, were incorporated to HA hydrogels and the release properties of HA hydrogels as a function of the degree of crosslinking were studied. The capacity to absorb water decreases dramatically with crosslinker concentration. The results showed that a more sustained release was obtained for HA hydrogels with a high degree of crosslinking. Furthermore, the MTT test was applied to study hydrogels toxicity and the influence of crosslinker concentration on HeLa human cells viability was determined. The results obtained on the release properties of HA hydrogels indicate that there are suitable for controlled drug delivery due to the possibility of modifying the crosslinking degree that influence release kinetics. Likewise, in vitro assays show that these materials could be considered as good candidates for implant developments due to their low cytotoxicity