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Preparation Of Smart Magnetic Drug Delivery Nanocarriers And Their Biological Evaluations

Posted on:2015-03-24Degree:DoctorType:Dissertation
Country:ChinaCandidate:J H LiFull Text:PDF
GTID:1224330422471428Subject:Biomedical engineering
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First attempt at the synthesis and application of engineered nanoparticles can betraced back to the early1950s of the20th century; nanotechnology had been witnessedgreat development over the past several decades. Nano-materials with smart quantumeffects compared to other normal materials, such as nano-scale effects, big surface areaand many new physical and chemical properties which pushed them to applicate inscience and engineering uses. After years of development, nano-science research hasmade considerable progress in material selections, dimensional nanoscale constructionsand intelligent applications. Meanwhile, a series of new breakthroughs and discoverieswere got by scientists in almost every field of science nowadays, nano-technology hadbeen widely used in industry, agriculture, medicine, environmental protection, military,energy and so on.Magnetic nanoparticle is one of the best engineering nano-materials, magneticmaterials itself has a unique excellent characteristics contrasted to any other material,the magnetism performance, which makes it could made quickly magnetic response toan external magnetic field. Herein, magnetic materials were used for magneticseparation and purification, hand sexual material detachment, cell/bacteria separation,enzymes immobilization, target drug delivery, stimulus-response controlled release andhyperthermia. However, nanomaterial especially inorganic compands usually hassome coexistence problems: while is how building special heterosexual surfacemodified sexual material and how to achieved target features; once used in vivo, thesafety of the material should be taken care, such as bloodcompatiblity,biocacompatiblity, rejection rand inflammation reaction, metabolism mechanisms in thetissues and organs and so on. These problems greatly hindered the development ofengineering nanoparticles for bio-usage.Base on the background above, our research focuses on the preparation andapplication of magnetic drug carrier. Meanwhile, intelligent design and biologicalevaluation were also need to give consideration. The magnetic nanocarrier includes thefollowing several uses: separation of harmful ingredients in blood, drug delivery andtumor hyperthermia. Finally we investigated the hemocompatibility, biocompatibility,particle distribution, transshipment in cells and tissues, metabolic pathways and clinicalanticancer effect. The main contents and conclusions of the study are listed as follows: 1. Preparation and characterization of magnetic nano-particles with different sizesIn this study, different scale magnetic nanoparticles were prepared by hydrothermaland template methods; then the functionalized magnetic beads were fabricated bysurface modifications for different specific biological application. Multiple testingmethods were also introduced to investigate the physical and chemical properties of theas-synthesis nanoparticles, such as the use of field-emission scanning electronmicroscopy and transmission electron microscopy to morphological characterization ofmagnetic particles, by vibrating sample magnetometers to study its magnetic properties,and so on. The obtained results show that magnetic nano-particles dispersed uniformparticle size distribution, regular shape and good magnetostatics properties for rapidmagnetic response. Crystalline of the magnetic particles can be confirmed by x-raydiffraction analysis which shows a typical spinel crystal structure compared to Fe3O4.2. β-Cyclodextrin conjugated magnetic nanoparticles for diazepam removal frombloodIn this chapter, β-Cyclodextrin conjugated magnetic nanoparticles that serve as ahemoadsorbent for diazepam removal are fabricated. The diazepam is arrested by theconjugated b-CD and then the adsorbed diazepam is efficiently removed by an externalmagnetic field. These particles have potential applications in hemoperfusion orseparation of other toxins and drugs. SEM and TEM images demonstrated that theas-synthesized magnetic particles had well dispersed morphology with round featuresand the average diameter of the particles was around200nm. The prepared Fe3O4particles had good bloodcompatibility and displayed a magnetization value of76.4emug-1which made it easy to be separated. For a3h period of absorption, around50.6%diazepam was eliminated by magnetic adsorbent; around54.9%diazepam was removedby activated carbon; whereas there was only around10%removal of diazepam byMNPs@APTES, the nanoparticles demonstrated great potential to be a novelhemoadsorbent for efficient removal of diazepam both from solution and plasma.Meanwhile, the β-Cyclodextrin conjugated magnetic nanoparticles reported here havepotential application in hemoperfusion or separation of other toxins and hydrophobicdrugs.3. Recyclable heparinized magnetic chitosan nanocomposites for selective removalof low-density lipoprotein from plasmaIn this chapter, we describe A new fabricate protocol is described to obtainheparinized magnetic chitosan nanocomposites as a blood purification material for removal of low-density lipoprotein (LDL) from plasma. Meanwhile, the adsorbent canbe easily separated completely by an external magnet for recyclable use since it has amagnetic core. The LDL level decrease by67.3%after2hours of hemoperfusion. Theused adsorbent become to be a newborn when washed with NaCl solution, even endureeight cycles, the removal efficiency is still above50%. This recyclable magneticadsorbent has good blood compatibility due to the heparin outside of the magneticnanoparticles, which can be used for LDL apheresis without significant side effects.The static adsorption of hyperlipidemia indicates that the heparin/chitosan modifiedmagnetic carriers shows high selective adsorption for low density lipoprotein in blood("bad" cholesterol), while the adsorption capacity of high-density lipoprotein ("good"cholesterol) is relatively smaller. After the adsorption process, the MNPs@Chi@Hepwas collected by a magnet and washed with gradient concentration chloride sodiumsolution to regenerate for a new cycle, in experience eight cycles application, themagnetic carrier still reveal quite good adsorption performance for low densitylipoprotein remocal.4. Phase-Change materials loaded hollow magnetic nanospheres for thermo-chemocombined therapyIn this chapter, A novel thermo-chemo collaborative cancer therapy system forloading either hydrophobic or hydrophilic drugs was obtained by introducing drugs andphase-change material (PCM,1-tetradecanol, melting point:38-39°C) into the interiorsof the hollow magnetic nanospheres. The system shows sensitive thermal responsewhen exposed to an alternating magnetic field (AMF) since its external magnetic shell,locoregional heat caused by AMF then triggers the local drug release with the meltedPCM to kill the hepatic tumor cells (HepG2) directly, the release efficiency of this drugcarrier could achieve above80%at42°C and less than5%at37°C. Meanwhile, wecan operate the system as “on” or “off” status by switching the alternating currentmagnetic field. This combination therapy presents more efficacious than hyperthermiaor chemotherapy alone which was verified by cell viability assays. Simultaneously,tumors grown in HepG2cell-bearing mice were also distinguished suppressed afterthermo-chemo combined treatment.
Keywords/Search Tags:Magnetic nanoparticles, magnetic separation, drug delivery, cancer therapy, tumor volume
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