| Nanoparticles drug delivery system is using synthetic polymer materials or biodegradable natural polymer materials as the carrier,to package and adsorption of drugs.Compared with single drug,the drug loaded nanospheres can increase therapeutic effects of prolonging the half-life of drug,reduce sediment in the potions and increase the solubility,quickly dissolve and have improved biocompatibility,so as to achieve better treatment effect and enhanced bioavailability.Nanoparticles drug system can realize the treatment and diagnosis reagent to achieve the best treatment effect,by transporting diagnosis reagent to the exact lesion site and reduce the side effect of drug treatment to a great degree.In view of this,graphene oxide was prepared by the improved Brodie method.Then carboxyl graphene oxide,with excellent hydrophilic property was combined with hydroxypropyl-beta-cyclodextrin to obtain different nano drug carrier,and their structures and properties were characterized.To further optimize the composition of the carrier,nanometer composite microspheres were prepared.We use this new type of nano drug carrier to load difficult soluble drugs,such as dexamethasone and Paclitaxel.Through combination of biochemistry experiments and modem tanalysis methods,the release mechanism of nano drug delivery system was clarified from the cellular and molecular level.Through experiments and research of this work,the concrete research content is as follows:(1)Nano drug carrier should has tihie characteristics of low toxicity,high efficiency,slow release,long-lasting and a certain activation and the promoting effect on drugs.We designed and synthesized a novel sheet-like carrier GO-COO-HP-p-CD with good blood compatibility.The thesis firstly using solid-phase grinding technology,having a hydrophobic drug cavity HP-p-CD intercalated into carboxyl graphene oxide layers.Part of the HP-?-CD reacted with the carboxyl of GO-COOH to graft to the surface of GO-COOH layer,part was connected by electrostatic attraction and hydrogen bonding.The XRD test results show that HP-?-CD was inserted to GO-COOH interlayer successfully,TGA results show that the GO-COO-HP-?-CD heat-resisting performance was greatly improved,Raman and FTIR test data further illustrate HP-P-CD can be grafted by ester bond to GO-COOH layer surface The obtained GO-COO-HP-?-CD was proved to be with good stability and blood compatibility(2)Since the non-spherical nanometer particles are vulnerable to external forces in blood vessel flow,glutaraldehyde was adopted as a crosslinking agent to cornvert GO-COO-HP-?-CD to micro particles,the size which was about 100 nm withIII microporous.XRD and FTIR results further confirmed that the crosslinking worked by ether bond.SCA and solubility experiments suggest that the nanometer microspheres designed.the GN good dispersibility.Analysis showed that the blood compatibility desigrned.the GN has good blood compatibility.MTT experiment results show that the cytotoxic levels of the material with the concentration range of 0.01-1000 ?g/mL are 0 or 1.That nidicates that the nanosphere was suitable for drug carriers.(3)In order to improve the low solubility in water of dexamethasone,we use the nanosphere GN to load dexamethasone.HPLC method was used to test the drug loading capacity and the encapsulation rate of dexamethasone in GN/DEX.The study found that with the decrease of the dexamethasone,the encapsulation rate increase gradually,and drug loading capacity reduces accordingly.In order to make the drug not waste,we choose DEX:GN=1:5(g/g).When DEX:GN=1:5(g/g),the drug loading capacity was 14.31%,the encapsulation rate was 71.55%,is 2.17 times of GO-COO-HP-?-CD and 6.88 times of HP-p-CD.FTIR results indicating that part of DEX connect with carrier through chemical bond.TG experimental results show that GN/DEX shows excellent heat resistance,good for drug processing,solubility experiment shows that GN/DEX has good dispersion.In vitro release experiments show that GN/DEX nanospheres released in the acidic environment is better.Experiment proves the biological activity of DEX from GN/DEX is well kept.Blood tests show that GN/DEX has good blood compatibility.The results of MTT experiment demonstrate that the material with the concentration range of 0.01-1000?g/mL,its cytotoxic levels are 0 or 1,showing that GN/DEX has no cytotoxicity.(4)How to maximize effectiveness and minimize the harm to human tissue cells caused by cancer drugs,has became a crucial problem in medical fields.The drug loading capacity and the encapsulation rate of GN/PTX were determined by enthalpy change.The study found that with the increatse of taxol inputs,the drug-loading rate of GN/PTX are first after rising downward trend,so PTX:GN=1:10(g/g)is more ideal.When PTX:GN=1:10(g/g),the drug loading capacity was 8.99%,the encapsulation rate was 89.90%,is 2.32 times of GO-COO-HP-?-CD and 3.22 times of HP-?-CD.FTIR results indicating that part of PTX connect with carrier through chemical bond.TG experimental results show that GN/PTX shows excellent heat resistance,good for drug processing,solubility experiment shows that GN/PTX has good dispersion.In vitro release experiments show that GN/PTX nanospheres released in the acidic environment is better.Experiment proves the biological activity of PTX from GN/PTX is well kept.Blood tests show that GN/PTX has good blood compatibility.Cytotoxicity experimental results show that the tumor inhibition effect of GN/PTX is 5-6 times to PTX,therefore provides a new anticancer drug carrier material the difficult soluble.Carrier microsphere with insoluble drug has an outstanding performance,indicating a broad application prospect.Although medicinal carrier has not been highly commercialized,but after so many years of development,remarkable achievements have been made.The author believes that,with the rapid development of this cross subject:polymer chemistry,pharmacy,and the fusion of life science,drag-loading nanoparticles will become one of the most efficient tool of clinical treatment,and the study of drug-loading nanoparticles will also become an important area in the field of medicine. |
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