Susruta Samanta

• Synthetic polymers are versatile materials with an extraordinary range of technological applications playing essential and ubiquitous roles in everyday life. Presently, the applications of polymers are not limited to traditional areas of technology but extend to novel uses in the areas of nanotechnology connected to medicine and pharmacology. Polyethylene oxide (PEO) and polypropylene oxide (PPO) homo-polymers as well as the block co-polymers based on them (Pluronics or Poloxamers) are among the most versatile polymers used in these fields. These polymers have the advantages of being non-toxic, easily available, economic and customizable to meet specific purposes. Despite many experimental and theoretical studies on them, the actual mechanisms of their interactions with bio-systems and drug molecules are still unknown. The research work reported in this PhD thesis is aimed to understand the behavior of these polymers in solution and their interactions with biological interfaces and drug molecules using molecular dynamics simulations. Recently proposed models for the ether based polymers and their monomers were successfully tested in a wide range of non-aqueous solvents to establish their versatility. The thermodynamics and kinetics of the polymers and the monomers were first studied at simple water/n-heptane interface. Eventually the research was extended to study their properties at lipid bilayer interfaces. The percolation behavior of the ether based polymers and their monomers were studied using standard molecular dynamics, steered molecular dynamics and umbrella sampling simulations. It has been shown that the percolation of PPO chains through lipid bilayer is favored compared to their PEO counterparts. PEO chains do not have any preference for the interior of the bilayer and but the PPO chains prefer to stay inside the bilayer. PPO chains with length comparable to the width of the bilayer tend to span across the bilayer. Pluronics also show similar effect with PPO parts spanned along the width of the bilayer and the PEO blocks in the polar headgroup region and water in both sides of the bilayer. The potential of mean force barriers of bilayer percolation were found to be smaller for PPO chains of all lengths than their PEO counterparts. The last part of the project aimed to investigate the mechanism of interaction of Pluronics with hydrophobic drug molecules. Curcumin, a natural drug from the Indian spice turmeric, has recently attracted interest as potential multivalent drug for the treatment of different diseases comprising cancer and Alzheimer's disease. For its hydrophobic nature, it has low solubility in water and therefore efforts are directed to find suitable polymeric carrier. For all these reason, Curcumin was chosen as model of hydrophobic drug for my study. A suitable force field model for this drug was optimized and used to study its interaction with Pluronics. The results of these MD simulation studies evidenced the mechanism of drug-polymer aggregate formation in which Curcumin is embedded into a hydrophobic PPO core surrounded by a hydrophilic PEO shell. The findings of this thesis are useful in the better understanding of the interactions of block co-polymers with bio-membranes at atomic level. Moreover, they provide a better insight on the dynamics and thermodynamics of the drug encapsulation and delivery across cell membranes.