Synthesis Of Star Poly(Ethylene Oxide) For Drug Carriers

Nowadays, polydimethylene ether (PDME, including PEG and PEO) has become an ideal drug carrier of micromolecule medications and protein, peptide drugs. Compared to linear polymers, star PDME, with special branched structure, has more interesting applied foreground since it's high mobility in vivo and low accumulation in body. This can promote the efficiency of the drug arriving at the target tissue and controlled delivery. Another prominent advantage of star PDME is that multifunctional groups exist in the ends, so it can carry more drugs and has the much longer circulation time in vivo as compared to linear onea. Presently, the branched PEG which has two chains of PEG attached to a core was studied more, but few researches on star PEG (PEO) were reported.In the thesis, the way which called "one step" polymerization was used to synthesize star PEO, that is to say multifunctional compounds were used as initiators or transfer agents to initiate ethylene oxide (EO) polymerization. Two initiate systems were adopted: alkali-polyols and Lewis acid-polyols. Through the control of reaction conditions, star PEO with the controlled molecule weight was obtained. The reaction mechanisms and product structures were also researched from the process of some elementary reaction steps of polymerization such as chain initiation, chain propagation, chain transfer and chain termination.Star PEO was obtained when the alkali-polyols initiate system used. But the molecule weight distribution of the product was wide and some linear PEO with low molecule weight were being in it. The homogeneous star PEO could be got through the separation way of column chromatography and the products processed by the way were fit for the use of drug carriers. Further more, polymerization products with different active end groups could be synthesized when the different termination ways were adopted. For example, when the terminator was H₂O, hydroxyl groups were the main end groups of the polymer; but when no any terminator used, then vinyl groups were the main ones. Polyols played two roles of chain initiation and chain transfer in polymerization process. These two actions all resulted in the formation of star PEO.In addition, in this thesis Lewis acid andβ-cyclodextrin (β-CD) has been adopted as initiate system to synthesize PEO at the first time and star PEO with high molecule weight was obtained too. The results also broke the rule that using cationic polymerization can't get PEO with high molecule weight. Three kinds of Lewis acid were observed, they are ZnCl₂, TiCl₄ and ZrCl₄ . The polymerization products with different structures were synthesized by the mole ratio change of Lewis acid toβ-CD. When the Lewis acid was TiCl₄ or ZrCl₄, crosslinked or part-crosslinked PEO was formed. All these crosslinked polymers could be transferred into star ones by the process of dissolution in HCOOH. In addition, through the mole ratio change ofβ-CD to EO, the star PEO with different molecule weight were obtained. The more important fact is many different polymerization products with all kinds of active end groups could be got easily by the use of different termination ways in theory. This can make PEO become a broader used drug carrier. Moreover, the polymerization mechanism was studied and the cationic coordination polymerization mechanism was presented by the analysis of lots of experiment phenomenon and results.