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Study On Polymer Delivery System For Brain Glioma Theranostics

Posted on:2018-12-23Degree:MasterType:Thesis
Country:ChinaCandidate:L HanFull Text:PDF
GTID:2334330512487188Subject:Pharmacology
Abstract/Summary:PDF Full Text Request
Modern clinical medical has developed gradually from the traditional"one-size-fits-all" to the new individualized treatment strategy.This treatment allows the doctor to minimize the time between diagnosis and treatment.Theranostics,integrates the diagnostic reagents and treatment reagents in a single system,this treatment strategy in the field of individual administration play an important role.Recent diagnostic reagents are non-invasive imaging molecules such as ultrasound,magnetic resonance(MR),computed tomography(CT),single photon emission computed tomography(SPECT)and so on.Anticancer drug,such as paclitaxel,doxorubicin,cisplatin is pretty popular.By taking advantage of their own properties,the combination of diagnostic and therapeutic agents play a synergistic effect,achieving real-time monitoring of the role of treatment feedback.At the same time,the diagnosis and treatment of integrated nanoparticles can be used as a tool to screen both safe and effective dose,so that the doctors in the early stages of the disease could avoid unreasonable use of drugs or side effects on the human body.Among the drug-delivery vichles,the polymer is the most popular platform for nano-diagnosis and treatment.In the process of cancer treatment,as a carrier platform system,the chemical-bond polymer could increase the solubility of free drugs and drug-loaded efficiency,and prolong the half-life of drugs in the body to ensure the release of drugs in the body.In addition,the size of the polymer increase EPR effect,achieving passive targeting.In addition to passive targeting,the polymer chain could also be connected to the active target molecules,accurate targeting of the lesion,so that drugs can be accurate and efficient delivery to the disease site.Although the above-mentioned polymer as the rapid development of nanoparticles carrier has many advantages,scientific studies still meet a lot of problems need to be resolved.Firstly,high cost Non-toxic safety contrast agents and expensive polymer materials,it is to say that,it increases the cost of research and development,many R&D laboratories do not have sufficient funds to finish large quantities of research,at the same time,the high cost of medical treatment lead lots of patients can't afford the costof expensive high-end drugs,and finally delay right time treatment at the early stage;Secondly,in the field of contrast agents,especially deeper level of research about the contrast agent itself and polymer molecules interaction whether could influence the physical and chemical properties is rare,which is particularly important in safty.Thirdly,the complicated preparation method,easily to destroy the drug itself functional groups,the incorporation of unnecessary impurities,and hardly repeated,are the most difficult problems we meet,directly influence the large-scale production.In order to solve the above problems,the design of a simple preparation,including high safety,good efficacy of the diagnosis and treatment of integrated nanoparticles,and the anti-tumor delivery system has a significance for the future of individualized areas of intensive research.The design idea of this topic is that the chemically bonded paclitaxel polyglutamic acid that can be self-assembled to form nanoparticles in water,and the nanoparticles are hydrophilic and internal hydrophobic to form a polymer drug loading platform.And then dissolved in the organic solvent contrast agent drop into the water phase,by phacoemulsification to make it into a clear solution,the two role in a unified system,and then remove the extra solvent,the final freeze-dried to form a theranostics nanoparticles PGGA-PTX/SPION.The multifunctional nanoparticles were chemically characterized by dynamic evaporative light scattering instrument,transmission electron microscopy,ultraviolet spectrophotometer and thermogravimetric analyzer.The CCK-8 kit,Prussian blue staining,H&E staining and so on were used.In vivo evaluation,it includes two aspects.On the one hand,the effect of this nanoparticle is evaluated by the nuclear magnetic resonance instrument.On the other hand,it is studied by tail intravenous on the efficacy of drugs.Through the series of experiments,the results show that the experimental preparation of the theranostics nano-particles have a good diagnosis and treatment function.In the physical and chemical characterization,pGGA-PTX/'SPION nanoparticles are plump and uniform in size,about 110um,leading to the passive targeting of tumor tissue through the EPR effect.The content-loaded of nanoparticles were about 27.66%,the contrast agent content was about 6.34%.In vitro evaluation,such as cell viability,the pGGA-PTX/SPION nanoparticle was similar to that of PTX,suggesting a good anticancer effect on tumor cells.In the H&E experiment,the nanoparticles did not impair the normal tissue and fully demonstrated its safety performance.In vivo imaging,through nuclear magnetic resonance,we can clearly see that the drug in the tumor body throughout the metabolic process,to achieve real-time monitoring of drugs.In vivo pharmacodynamics experiment,the theranostics nanoparticle group shows a significant tumor growth inhibition effect.In summary,we have prepared the diagnosis and treatment of integrated nanoparticles.In the future,combination of tumor diagnosis and treatment could play an important role in clinical research,providing a safe,effective and feasible scientific study ideas.
Keywords/Search Tags:Polymer delivery system, diagnosis and treatment nanoparticles, contrast agent, PTX
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