The Study Of Glucose-Responsive Polymer With Different Topo Structures Based On P -Enylborate Ester:Sythesis And Properties

This paper improved the structure of the phenylborate ester series polymer based on the previous work of our research group and the actual needs in order to enhance the stability of the self-assembled system when responsing glucose and glucose selectivity and biocompatibility of the nanoparticals.As the properties of polymer depends on its structure to a large extent, We desi-gned polymers with different topo structures, the properties of the polymer were improved by two kinds of strategies:one was to synthesis brush polymer; the other was to introduce cholesterol monomers with special properties, thus introducing special properties to the self-assembled system of the polymer.1. Compared with traditional linear polymers, amphiphilic brush-like glucose-responsive blockpolymer with brush-typed hydrophobic segment which has obvious advantages. A series of brush polymers MPEG5000-b-(PCL-g-PPBDEMA) with different numbers of units and appropriate PDI were sythesized through designing followed by characterization of NMR and GPC. The behavior of self-assembly and insulin encapsulation was researched by DLS, TEM and FL, finding that the brush polymer has stronger self-assembly driving force and stronger ability of insulin encapsulating. Then we researched systematically the glucose-responsive behaviour of the polymers from glucose selectivity, intelligence and controllability of insulin-release partically, finding that the glucose-responsive behaviour has improved significantly compared with the previous work. Due to the introduction of hydrophobic PCL fragment to polymer main chain, we also studied the enzymatic degradation experiments finding that the polymers can be degraded completely under the lipase catalysis.2. Cholesterol is a strong hydrophobic liquid crystal molecule. Random or block glucose-responsive polymers with cholesterol segments were obtained by introducing cholesterol. When self-assembling in water the cholesterol segments and the phenylborate ester segments consist in the core which the phenylborate ester segments work as glucose-responsive part while the cholesterol segments can stabilize the nanoparticles. A series of amphiphilic random copolymers based on different cholesterol and phenylborate ester monomers were synthesized followed by the study of the self-assembly behaviour and liquid crystalline behavior, and finally the glucose-responsive behaviour under different conditions of different polymer systems was studied. No obvious improvement to the system impairment was found. The random copolymer can be dispersed cholesteric liquid crystal properties, the liquid crystal properties of polymer is not obvious. The single introduction of hydrophobic property of the cholesterol monomer to polymer is not able to enhance the glucose-responsive controllability, andvthe liquid crystal property may be necessary to be introduced.3. In this chapter we designed an ABCBA-type pentablock copolymer, A stands for polycholesterol segmnet, B is for phenylborate ester glucose-responsive segment, and C represents MPEG4000. The hydrophobic terminals of polymers with such structure aggregated into hydrophobic core, forming flower-like micelles in water. At the same time, the A block with the properties of liquid crystal can arrange to a certain sequence, which can physically cross-link in the hydrophobic core bringing strong force stablizing the nanosystem in addition to the strong hydrophobic force of the cholesterol. The pentablock copolymer was synthesized through two steps of ATRP and characterized by NMR and GPC. Then the liquid crystalline properties were characterized by DSC, which exhibited obvious liquid crystalline properties. The concentration of 0.25 mg/mL was utilized to study the behaviour of self-assembly and insulin-capsulation and glucose-responsive behaviour. We found that the glucose selectivity and the controllability under normal glycemia were improved substantially. Besides, this system adopted lower polymer concentration to capsulate insulin through self-assembling, which can greatly enhance the drug load rate on the premise of ensuring stability and good responsive releasing behavior.