(575f) Engineering Lipid Nanoparticles to Mitigate Oxidative Stress in Stem Cell Transplant Therapy

The cell transplant and organ transplant therapies have been widely used for several applications in medicine. The integrity of the transplantation process is highly dependent on cell adhesion, migration and proliferation. However, the reactive oxygen species (ROS) generated in surroundings during this process inhibits the cell-cell and cell-matrix adhesion, affect cell spreading and lead to increased detachment of cells. Reactive oxygen species can also induce an inflammatory response thereby damaging the cellular structure and function and leading to cell death. Thus the survival rates of cells when transferred in vivo are very poor because of the oxidative stress that they experience. Pre-treatment of cells with antioxidant prior to the transplant process can help in increasing the survival rate of cells. Vitamin E can be used as a potential drug owing to its antioxidant properties. Targeted drug delivery using nanoparticles has several advantages over the traditional drug delivery method such as reduced dosage of drug, lesser side effects, decrease in cost of therapy and increased accumulation of drug within the target tissue. Liposomes are very biocompatible and highly tunable for specific applications. Thus the vitamin E loaded lipid nanoparticles can be efficiently used for targeting the site of oxidative stress. In this project, we are developing highly customizable lipid based nanoparticles encapsulating vitamin E for targeting the site of oxidative stress. We have engineered lipid nanoparticles (LNPs) of various sizes, surface charges, and coating density of hydrophilic polymer using non-cationic lipid and cholesterol components. LNPs were characterized by both photon correlation spectroscopy to determine particle size distribution, hydrodynamic diameter, and polydispersity, and by zeta potential measurements to determine nanoparticle surface charge characteristics and to quantify colloidal stability. The encapsulation studies were performed using the absorbance measurement of vitamin E at 295nm wavelength and we obtained upto 75 % of encapsulation efficiency. The preliminary uptake studies using stem cells and FITC tagged LNPs indicated that the nanocarriers were internalized into the cytosol. Then the stem cells were treated with peroxide (H202) at different concentrations to create an oxidative stress environment. The vitamin E loaded LNPs targeted to these cells showed a significant decrease in the reactive oxidative stress induced due to peroxide. We are currently examining the release kinetics of vitamin E from the LNPs. The future work of this research involves optimisation of the process along with the in-vivo studies of stem cell transplantation in mice.