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Preparation And Application Of Degradable Environmentally Responsive Nanogels

Posted on:2022-07-09Degree:MasterType:Thesis
Country:ChinaCandidate:M LeiFull Text:PDF
GTID:2491306569455994Subject:Materials engineering
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Traditional cancer therapies mainly include surgery,chemotherapy,radiotherapy and other methods.Although these therapies have certain anti-tumor effects,their clinical applications are greatly limited due to their large side effects,easy recurrence,and non-targeted treatments.Nanogels have received extensive attention in the field of drug delivery due to their nanometer size,high structural integrity,high water swelling properties,and versatility.Among many nanogels,smart nanogels can change the particle size,morphology,and hydrophilicity and hydrophobicity under external environmental stimuli,which has become a research hotspot in the field.In recent years,researchers have greatly promoted the development of smart nanogels through in-depth research on stimulus-responsive nanogels,making them play a huge role in the field of tumor treatment.This paper explored biodegradable stimulus-responsive nanogels,with the aim of enabling them to achieve targeted drug delivery and have better anti-tumor effects.The specific research work is as follows:(1)Using N-vinylcaprolactam(VCL)and 2-(methacryloxy)ethyl dimethyl-(3-sulfopropyl)ammonium hydroxide(DMAPS)as polymerization monomers,a novel biodegradable zwitterionic nanogel with temperature sensitivity and redox degradability was prepared by aqueous precipitation polymerization.The nanogel has good temperature stimulus responsiveness,and can exhibit sensitive temperature-induced swelling/collapse behavior in an aqueous solution.The presence of the disulfide bond cross-linking agent allows the nanogels to undergo degradation behavior under reducing conditions;In vitro drug release experiment proved that the drug release amount of the nanogel in a reducing environment was much higher than normal physiological conditions,and showed excellent selective drug release behavior.In vitro cytotoxicity experiments show that the drug-loaded nanogel has a significant tumor cell killing effect.(2)We fabricated a new type of zwitterionic nanogel with dual redox-labile properties by copolymerization of 2-methacryloyloxyethyl phosphorylcholine(MPC)and a diselenide bond-containing crosslinker through reflux precipitation polymerization.Poly(2-methacryloyloxyethyl phosphorylcholine)(PMPC)-based nanogels show high protein adsorption resistibility and colloidal stability at high salt concentrations.By incorporation of diselenide bonds into polymer networks,the nanogels are endowed with unique dual redox-labile properties that lead to their efficient degradation into short polymers either in a reducing environment or in an oxidative environment.Nanogels loaded with anticancer drugs(doxorubicin,DOX)display a finely controlled release behavior and low leakage of DOX under physiological conditions,but rapid and sufficient release under reducing conditions or under oxidative conditions.Cell viability assays reveal that the blank nanogels have no cytotoxicity within a wide concentration range,while drug-loaded nanogels present a significant inhibitive effect against tumor cells.
Keywords/Search Tags:Drug delivery system, Biodegradable, Nanogels, Temperature-responsive, Redox-responsive
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