Abstract (EN):
The use of polysulfone (PSU) hemodialysis (HD) membranes modified with bioactive compounds has gained relevance in chronic kidney disease (CKD) management. Compounds based on the 4-oxo-beta-lactam scaffold have outstanding inhibitory ability and selectivity for human neutrophil elastase (HNE). The present work aimed to evaluate the bioactivity and biocompatibility of PSU-based HD membranes doped with HNE inhibitors (HNEIs). For this, two 4-oxo-beta-lactam derivates (D4L-1 and D4L-2) synthesized in house were used, as well as a commercial HNEI (Sivelestat), for comparison purposes. Their HNE inhibition efficacy was evaluated in in vitro and ex vivo (incubations with human plasma) assay conditions. All biomaterials were bioactive and hemocompatible. The inhibitory capacity of the HNEIs and HNEI-PSU membranes in vitro was D4L-1 > D4L-2 > Sivelestat and D4L-2 > Sivelestat > D4L-1, respectively. In ex vivo conditions, both HNEIs and HNEI-PSU materials presented the same relative inhibitory ability (D4L-1 > D4L-2 > Sivelestat). The difference observed between in vitro and ex vivo conditions is most likely due to the inherent lipophilicity/hydrophobicity of each HNEI influencing their affinity and accessibility to HNE when trapped in the membrane. Compared to Sivelestat, both D4L-1 and D4L-2 (and the respective doped membranes) have more potent inhibition capabilities. In conclusion, this work reports the successful development of PSU membranes functionalized with HNEIs.
Language:
English
Type (Professor's evaluation):
Scientific
No. of pages:
20