Chitosan nanoparticle diallyl disulfide complex immobilized polysulfone hollow fibre membrane performance for hemodialysis

Abstract

Aside from the low-flux issue, biocompatibility of hemodialysis membrane is another leading cause of mortality among end-stage renal disease (ESRD) patients due to increased oxidative stress and thrombus formation that led to cardiovascular disease (CVD). Hence, the main objective of this study is to develop an antioxidant and antithrombotic polysulfone (PSF) based hollow fibre membrane (HFM) for effective uremic toxins removal. A hydrophilic chitosan nanoparticle (CNP) was first synthesized via ionic gelation method. Using diallyl disulfide (DADS), a novel CNP/DADS complex was formed through simple complexation steps with ionic gelation method. The formation of the nanoparticle complex was confirmed by 1H nuclear magnetic resonance (H-NMR), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), differential scanning calorimetry (DSC), X-ray diffraction (XRD) and UV–Vis. An antioxidant, biocompatibility and antithrombotic properties were conducted, where the effect of DADS addition was evaluated. Both CNP and CNP/DADS showed antioxidant activity where the scavenging capacity against nitric oxide (NO) and hydrogen peroxide (HP) was superior in 1.0 mg/ml CNP/DADS with 29.4% and 32.8%, respectively. CNP/DADS showed a low hemolysis rate of <1% and complement the C3a and C5a activation that demonstrated its biocompatibility. The prolonged APTT and PT with no observation of platelet aggregation as compared to CNP also demonstrated the CNP/DADS antithrombotic properties. In the next step, 0.1 wt.%, 0.3 wt.% and 0.5 wt.% of CNP and CNP/DADS were immobilized into PSF. The HFM were spun with different spinning air-gap. The result showed that PSF HFM with 0.3 wt.% CNP spun at 50 cm air-gap produced the highest KUF of 116 ml/m2.h.mmHg, 95.7% BSA rejection and 85% of urea, creatinine 66%, and lysozyme 43% clearance. The promising results were due to the increased in hydrophilicity and improved morphological structure of the membrane with higher porosity and thinner membrane skin layer. At a higher CNP concentration of 0.5 wt. %, the KUF value of HFM dropped by 23% which was affected by a thicker outer skin layer and lower porosity. Compared to CNP immobilized PSF HFM, CNP/DADS immobilized PSF HFM showed a reduction in KUF value due to poorly dispersed agglomerated nanoparticles that created denser HFM morphological structure. Nevertheless, the membrane performances still meet the high-flux standards. The CNP/DADS immobilized PSF HFM demonstrated enhanced biocompatibility by exhibiting a lower hemolysis rate of <1%, lower protein adsorption and platelet adhesion and induced less complement C3a and C5a activation. It also significantly (P<0.001) prolonged APTT and PT test value which indicated the enhancement of antithrombotic properties. The CNP/DADS also promoted higher antioxidant properties for PSF HFM compared to CNP. The CNP/DADS immobilized PSF HFM displayed higher antioxidant activity against nitric oxide and hydrogen peroxide, by having scavenged percentages of 26.7% and 20.6%, respectively, compared to CNP with 4.1% and 2.7%. The findings of this study evidenced that PSF HFM with excellent antioxidant and antithrombotic properties has been successfully developed. The membrane can be potentially used for the safe and effective removal of uremic toxins in hemodialysis.