Synthesis, Characterization And Application Of Polymers Based On Poly(ethylene Oxide)

Poly(ethylene oxide) (PEO) is one of the most popular biocompatible polymers. It possesses an ideal array of properties: very low toxicity, excellent solubility in aqueous solutions, extremely low immunogenicity and antigenicity. Drugs can be chemically modified with PEO or lodded in the nanoparticles with PEO corona and reach long-circulating half-lives and excellent pharmacokinetic and biodistribution behavior. Yet the second generation Pegylation is focused on protein and peptide. As one method of the second generation Pegylation, branched PEO has been used to modify low molecular weight drugs rarely. However, the PEO modified liquid-core nanocapsules are difficult to be functionalized and the loading content by polymer micelles is not high. We try to find a novel method to prepare liquid-core nanocapsules with high loading content and varied functionalities. The main results have been obtained as follows:1. Monomethoxy-polyethylene oxides (mPEOs, Mn= 2000, 3000, 4700) were synthesized and the terminal hydroxyl group was converted to carboxyl group with high efficiency, and then mPEO-COOH was obtained. Two-arm branched PEO (mPEO₂) with different molecular weight (M_n=4000, 6000, 9400) were synthesized by coupling the carboxyl groups of mPEO-COOH with the amino groups of one lysine molecule. Then the obtained branched polymer was used as carrier for immobilization of cisplatin (cis-diammine (dichloro) platinum (II), CDDP). As a contrast, CDDP modified with linear mPEOs were also synthesized. All these polymeric drugs modified with branched PEO are water soluble and show higher cytotoxic activity against C6 human breast cancer cells than cisplatin modified with linear mPEO with the same molecular weight. All the polymeric CDDP showed the much lower toxicity than the CDDP.2. The hydrophilic copolymers poly[(ethylene oxide)-co-glycidol] [poly(EO-co-Gly)] was prepared by anionic polymerization of ethylene oxide (EO) and ethoxyethyl glycidyl ether (EEGE) first, then the hydroxyl groups on the backbone were recovered after hydrolysis and partly modified by hydrophobic conjugated linoleic acid (CLA). The copolymer with multiple linoleate pendants was absorbed at the oil/water interface and then crosslinked to form stable nanocapsules. The mean diameter of the nanocapsule was below 350nm and the size distribution was relatively narrow (<0.2) at low concentration of oil in acetone (<10 mg/mL). The particle size could be tuned easily by variation of the emulsification conditions. The nanocapsule was stable in water for at least 5 months, and the shell still kept integrity after removal of the oily core by solvent. Pyrene was encapsulated in these nanocapsules and high loading efficiency as 94% was measured by UV spectroscopy. Thus a convenient approach to prepare the liquid-core nanocapsules by cross-linking amphiphilic copolymer at oil-water interface was provided.3. Poly(ethylene oxide)-block-poly[2-(dimethylamino)ethyl methacrylate] (PEO-b-PDMA) was synthesized by ATRP polymerization of DMA using PEO-based macroinitiator. Then the DMA units of the block copolymer were partly modified with bromooctadecane. The obtained amphiphilic copolymer was absorbed at the oil/water interface and to form stable nanocapsules, the cross-linking procedure was performed by adding 1,4-dibromobutane and the efficiency was estimated by ¹H NMR. The pH-responsive properties of the capsules were investigated. When the pH of the dispersion decreased to 3, the diameters of the nanocapsules increased sharply. Capsules with different core/shell mass ratio showed the different PH-responsive properties, the larger the core/shell mass ratio, the higher the diameter increase, and the maximum change of the diameter was 80nm. The cross-linking degree also affects the increasing degree.