(42ai) Development of Improved Polysulfone Based Hemodialysis Membranes by Using Temperature and pH Responsive Pentablock Copolymers

Introduction:
Polymeric membranes intended for hemodialysis applications have been attracting major attention in the medical field and have a huge place in the market. Polymer based hemodialysis membranes are expected to show outstanding blood compatibility, oxidative, thermal and hydrolytic stability, and high permeability for low molecular weight proteins as well as good mechanical and film-forming properties for an efficient operation and the comfort of the patient. However, the inadequate blood compatibility of current membranes entails the injections of anticoagulants during hemodialysis. In addition, the significant amount of reactive oxygen species, generated during hemodialysis, react with the proteins and lipids in blood causing oxidative stress which leads to cardiovascular, cancer, and age-associated neurodegenerative diseases. As a result, antioxidants are administrated to hemodialysis patients orally or intravenously [1, 2]. Therefore, the motivation for the present work is a need for the development of functional hemodialysis membranes possessing improved blood compatibility and suppressed oxidative stress. For this purpose, we propose the use of temperature and pH responsive amphiphilic pentablock copolymer family blended in with polysulfone (PSF) membranes. The temperature responsive Pluronic F127, consisting of polyethylene oxide - polypropylene oxide - polyethlylene oxide (PEO-PPO-PEO) blocks, constitutes the middle block while the pH responsive 2-N,N-(Diisopropylamino)ethyl methacrylate (DiPAEM), tertbutylaminoethylmethacrylate (tBAEM), N,N-(Dimethylamino)ethyl methacrylate (DMAEM), or N,N-(diethylamino)ethyl methacrylate (DEAEM) blocks form the end blocks for each member of pentablock copolymer family. The pentablock copolymers are blended in PSF matrix and alpha-lipoic acid (ALA), an antioxidant used for prevention of various chronic diseases associated with oxidative stress, is electrostatically immobilized on both surface and cross section of the membrane. These pentablock copolymers are being investigated in hemodialysis applications for the first time.
Experimental:
The PDEAEM, PDMAEM, PtBAEM and PDiPAEM pentablock copolymers were synthesized via atom transfer radical polymerization (ATRP) with the Pluronic macrointiator as described in our previous work [3]. PSF membranes were obtained by dry wet phase inversion technique and characterized by scanning electron microscopy (SEM). The antioxidant activities of immobilized ALA are measured using the free-radical scavenging activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) radicals. The blood compatibilities of the membranes are evaluated in terms of inhibition of reactive oxygen species in blood plasma, amount of adsorbed plasma proteins, platelet adhesion, activation and cytotoxicity on blood cells. The transport and structural properties of the membranes are also characterized.
Results and Discussion:
The NMR results depicted that pentablock copolymers were successfully synthesized. Our results indicated that the blending of pentablock copolymers did not block the pores and did not cause a significant difference in the classical finger-like structure of the PSF membranes which is preferable for maintaining the transport properties of the membranes. The protein adsorption results indicated that as the pentablock copolymer percentage in the casting solution increased the adsorbed protein amount on the membranes decreased. It was anticipated that the Pluronic F127 middle block prevents the protein adsorption through the temperature responsive micellization on the membrane surface and cross section.
Conclusion:
The use of proposed pentablock copolymers along with ALA in PSF hemodialysis membrane applications appears promising
References:
1. Ran, F., et al., Biocompatibility of modified polyethersulfone membranes by blending an amphiphilic triblock co-polymer of poly(vinyl pyrrolidone)–b-poly(methyl methacrylate)–b-poly(vinyl pyrrolidone). Acta Biomaterialia, 2011. 7(9): p. 3370-3381.
2. Mahlicli, F.Y. and S.A. Altinkaya, Immobilization of alpha lipoic acid onto polysulfone membranes to suppress hemodialysis induced oxidative stress. Journal of Membrane Science, 2014. 449(0): p. 27-37.
3. Determan, M.D., et al., Synthesis and characterization of temperature and pH-responsive pentablock copolymers. Polymer, 2005. 46(18): p. 6933-6946.