The Synthesis Of Phosphatidylinositol Polyethylene Glycol Monomethyl Ether And Its Self-assembled Micelles

Micelles with core-shell structure formed by amphiphilic copolymer in aqueous solution can be used as the carrier of hydrophobic drugs for targeted drug delivery and drug release. Polyethylene glycol (PEG) with characteristics of neutral, non-toxic and good biocompatible, find a wide range of applications in pharmaceutics. Phospholipid as composition of biofilm has good biodegradable and biological compatibility. So combined PEG and phospholipid to form PEG-lipids will possess combined advantage than its components, which has showed wide application in pharmaceutics. But expensive value has hampered its wide range of applications to some extent. Under this backgrounds, we design and synthesized a novel type of PEG-lipid, and investigated their self-assemble behavior and related influent factors. In this thesis two parts were reported: one is material synthesis, the other is physical behavior study.In the first part, we synthesized a series of amphiphiles with methoxy (Polyethylene glycol) [MW1000 (mPEG1), 2000 (mPEG2), 3000 (mPEG3), 5000 (mPEG5)] as a headgroup and diacylglycerol (2C₁₂, 2C₁₄, or 2C₁₆) as tail part, connected together by phosphorus oxychloride as linker. MPEG-lipids purification was conducted by dialyzing self-assembly lipids. And the products were characterized by MS, HNMR, IR, etc.The micelles were prepared by solvent evaporation method, and studied by the fluorescent probe, scanning electron microscopy, transmission electron microscopy, Zeta PALS-submicron size and potential analyzer. The results showed that the mPEG-lipids formed spherical micelles with core-shell structure and the diameter of 100～200nm. The CMC increased with the growth of the molecular weight of hydrophilic PEG for the same hydrophobic tail group, while the CMC decreased with the extension of hydrophobic chain length for the same hydrophilic head group. Compared to the small molecules surfactant, mPEG-lipids micelles have better stability in water due to the lower CMC of 10^-6mol·L^-1. The influent factor such as ionic effect and hydrogen-bonding on micelle formation was studied. The results showed that the size decreased with the increase of the concentration of sodium chloride and increased with the increase of the concentration of glucose. This is due to the interaction of ion with ionophore of PEG and salt effect on the aggregation of hydrophobic part. Hydrogen bonding effect by the saccharide is due to the interaction with PEG. So these change the balance of hydrophobic and hydrophilic in the lipids ensemble system.