Synthesis And Properties Of Block Copolymers With PCL Base Temperature And Reduction Responsiveness

Stimuli-responsive polymers have important research value in controlling the release and delivery of drugs,gene transfer,cell growth separation,catalyst carrier,artificial muscle and so on.Redox responsive polymers are one of the most studied polymers because of the redox reactions that occur in most of the materials in the body.With the increasing demand of human being,the synthesis and properties of temperature and reduction responsive block polymers have been studied.Polycaprolactone(PCL)is a kind of hydrophobic aliphatic polyester with good biocompatibility and biodegradability.It can be used as a hydrophobic block and can be self-assembled micelles of core-shell structure with hydrophilic block in aqueous solutions,the hydrophobic drugswere wrapped in the hydrophobic PCL core,drugs can be quickly and effectively released in the body of drug delivery and cell targeting.Under the physiological environment,PCL can be degraded under the hydrolysis of enzymes.Based on the excellent properties of PCL,polymers containing PCL blocks have been used in the fields of drug delivery vectors,tissue scaffolds and nanocrystal imaging.2-(2-methoxyethoxy)ethyl methacrylate(ME02MA)is atemperature responsive monomer containing an oligo(ethylene glycol)side chain,it has good water solubility and biocompatibility as PEG analogues.N-methylolacrylamide(HMAM)is a water-soluble monomer containing hydroxyl and amide groups.The LCST of PMEO2MA is 26℃.The addition of HMAM not only regulates the LCST of the block copolymer P(MEO2MA-co-HMAM),but also the amide groups can make the polymers applied to the human body.2-hydroxyethyl disulfide(SS-DOH)is a compound containing the disulfide bond,and itsadditions allow the block copolymer to have reduction-sensitivity.In this paper,the triblock copolymers P(MEO2MA-co-HMAM)-b-PCL-SS-PCL-b-(MEO2MA-co-HMAM)were prepared by the temperature responsive monomer MEO2MA,the hydrophilic monomer HMAM,the hydrophobic monomer PCL and the reduction responsive monomer SS-DOH.The solution properties,micellization behavior and sol-gel transition behavior of this triblock copolymer were studied.The blockcopolymer micelles and loaded-DOXblock copolymer micelles were prepared and the drugs releaseand antitumor behaviors in vitro of them were studied.Specific research work is as follows:1.The temperature and reduction dual-responsive triblock copolymers(ME02MA-co-HMAM)-b-PCL-SS-PCL-b-(ME02MA-co-HMAM)was prepared by ring-opening polymerization(ROP)and atomtransfer radical polymerization(ATRP),The LCST of the copolymer was adjusted by changing the feed ratio of the two monomers in the block P(MEO2MA-co-HMAM).Firstly,the synthesis of triblock copolymers was confirmed by FT-IR and1HNMR.The results of gel permeation chromatography(GPC)showed that the block copolymers synthesized using ATRP had a controlled molecular weight and molecular weight distribution of PDI<1.36.The temperature sensitivity of the triblock copolymer was studied by measuring the change of light transmittance of the block copolymer at different temperatureand the low critical solution temperature LCSTs of the copolymers under different conditions such as different concentrations,thepolymerization degree and two kinds of feed rates of monomers was studied.The measurements of the CMC,dynamic laser light scattering(DLS)and transmission electron microscopy(TEM)of the block copolymers was used to study the micellization behavior.Low CMC value of micelles is favorable for the delivery of drugs in the human physiology.DLS datas confirm the change of the particle size of micelles at different temperatures.The digital photographs of transmission electron microscopy show the process of temperature-induced block copolymer in forming core-shell structure of micelles.Finally,dynamic rheologicalmeasurement and a test vial inverting methodstudied sol-gel transition of the triblock copolymer.2.Thetemperature and reduction dual-responsive block copolymerssynthesized in second chapter were used to prepare the micelles of triblock copolymers and loaded-DOX of the micelles of the triblock copolymers.The change of particle size and fluorescence intensity of them were studied by adding different concentrations of DTT.The drugs rapid release behavior of the loaded-DOX block copolymers micelles by DTT in vivo was studied.Finally,the cytotoxicity of blank and loaded DOX block copolymer micelles were studied by MTT experiment.The results showed that the cell viability reached 93%when the concentration of blank micelles was as high as 1 mg/mL,indicating that the block copolymer micelles had good biocompatibility.The cytotoxicity of the loaded-DOX block copolymers micelles pretreated with 5 mM DTT showed the cell inhibitionis higher than free doxorubicin and untreated micelles.In a word,the amphiphilic block copolymers micelles with reduction sensitivity are used as an efficient drug carrier in biomedical and clinical medicine.