The prolonged contact of blood with the synthetic polymeric surface in hemodialysis leads to two very important long term complications viz., dialysis induced oxidative stress (DIOS), and membrane induced inflammation (MII). Therefore an attempt was made in this dissertation to fabricate hemodialysis membranes that were modified with phytochemicals, which could potentially reduce both DIOS and MII. Phytochemicals are non-nutritive plant-derived chemicals that are reported to have multiple disease preventing properties. Mangiferin, a phytochemical derived from mango tree and genistein, which is a soy-bean derived phytochemical were chosen based on superior anti-oxidant and anti-inflammatory properties. Membranes were decided to be modified by solution blending of phytochemicals with the polymer solution (physical modification) used to fabricate the membranes.
Miscibility characteristics of poly(amide)/poly(vinyl pyrrolidone)/mangiferin and poly(ether sulfone)/poly(vinyl pyrrolidone)/mangiferin blends were established. Membranes were cast in form of film via non-solvent induced phase separation process. Here DMSO was employed as solvent and water was employed as non-solvent. Unmodified membranes typically showed a dense skin layer while the cross section showed finger-like channel which progressively increased in diameter along the thickness. This gradient morphology ensures sufficient pressure gradient for the toxins to
be removed from the blood to the dialysate stream. Mangiferin modification of PA membranes led to an increase in surface porosity of the membranes whereas PA/PVP/mangiferin membranes not only showed microporous surface but also network structure. Membrane modification was also performed with genistein. Even at very low genistein concentration embedded crystals were observed on the membrane surface. As the concentration of genistein increased large spherulitic structures evolved on the membrane surface.
The anti-oxidant properties of pure phytochemicals, unmodified membranes, as well as modified membranes were measured. The author volunteered himself for donating the blood samples. The unmodified membranes were demonstrated to increase the reactive oxygen species (ROS) generation, which lent support towards the idea of DIOS. DHR assay with pure mangiferin showed an increase in the ROS levels at low concentration range (25-200 µg/ml) and a reasonable decrease (20%) at very high concentration range (500-1000 µg/ml). As a result, the mangiferin modified membranes (both PA/mangiferin as well as PA/PVP/mangiferin membranes) showed enhanced intracellular oxygen radical generation compared to that of the unmodified membranes. On the other hand, genistein modified membranes showed suppression of ROS levels in a dose dependent manner. It was hypothesized and experimentally confirmed that the presence of glucose in mangiferin might be one of the reasons for the observed increase in ROS levels. Measurement of cytokine profiles revealed that genistein modified membranes were effectively able to suppress the levels of IL-1β, IL-6, and TNF-α compared to that of mangiferin modified membranes.