Stimuli-responsive Hyperbranched Polymer Synthesis And Applications

In recent years,stimuli-responsive polymers have become more and more widely used in the fields of biology and medicine.Different topologies and different stimuli-responsive polymers have caused more and more attention.Among them,hyperbranched polymers have the characteristics of low viscosity,high rheology,and high solubility.Their high branching and three-dimensional structure can form enough space voids to encapsulate small molecular guests,and a large number of groups at the end can be further functionalized.In addition,they can self-assemble into nanomicelles at relatively low critical micelle concentrations.The introduction of stimuli-responsive hyperbranched polymers formed by stimulus-responsive groups in hyperbranched structures has great application potential in the field of biomedicine,especially as a controlled drug delivery vehicle.However,due to the complex design and the need to improve biocompatibility,today's drug carriers are difficult to apply to the clinic.In order to promote the further development of drug delivery and meet the different needs for drug delivery under different conditions,we designed two different stimulus-responsive hyperbranched polymers and studied their responsiveness.1.We prepared hyperbranched polymer micelles with ROS stimulus response based on lipoic acid.It can self-assemble in water to form a micelle structure.We use a thioether bond in the main chain to construct a redox system.The resulting micelles are stable under low pH conditions of the gastrointestinal tract and have ROS responsiveness.After reaching the intestinal tract,under the high H2O2 concentration environment of the target inflammation site,the hydrophobic-S-in the polymer is converted into hydrophilic sulfones and sulfoxides,causing the overall hydrophilicity of the micelles to increase and the micellar structure to be affected.When it is destroyed,the loaded drug is released,thereby achieving the targeted release of the drug.We used ultraviolet and transmittance changes to characterize its in vitro release.The results show that the hyperbranched drug-loaded micelles have good drug-carrying capacity,excellent H2O2 response,and sensitive drug release.The DSS-induced ulcerative colitis model was used to test the changes in body weight,DAI and MPO index of the mice and to further characterize their therapeutic effects by colon length,spleen index and intestinal tissue injury score.The results show that it has a good therapeutic effect on DSS-induced ulcerative enteritis.At the same time,we tested the changes of TNF-?,IL-1? and IL-6 inflammatory factors and NF-?B during treatment by PCR-directed reverse transcription,and further explored its anti-inflammatory mechanism.This hyperbranched with acid resistance and redox responsiveness has broad application potential in the field of oral administration.2.Hyperbranched polyesters with multiple stimuli response and good biocompatibility and degradation performance were prepared by one-pot method.The presence of tertiary ammonia,carbon chain backbone and ester groups gave them pH and temperature dual stimulus response,and Responsiveness is significantly different at different pH environments.We have characterized the structural changes of polymers by using their transmission changes under acidic or alkaline conditions and 1H-NMR.At the same time,we tested the change in the transmittance of the polymer under temperature rise and temperature and found that the dissociation process can be greatly accelerated at acidic pH.We have tested the cycling stability by changing the transmittance under repeated pH cycles of different pH conditions.The results show that the stability will decrease significantly under acidic and alkaline conditions.In view of the complexity and variability of the microenvironment in vivo,this hyperbranched polyester material with multiple functions has certain application potential as a drug delivery.