| In recent study,the design strategy based on the targeting of receptor mediated ligand and environmental sensitivity responsing shows strong advantages that improves selectivity and antitumor effect of nanocarrier.Ligands in nanocarrier surface,the specificity in tumor cells or endothelial cells surface receptors,can help carrier to distribute targeted in tumor tissues,and the efficient uptake of tumor cells is increased.In addition,the use of the tumor microenvironment of biological stimulation or external environmental stimuli(such as pH,temperature,enzyme,light,etc.)to design environment sensitivity nanocarrier,specificity uptake and release can be realized in the tumor tissue.To design resonably a preparation of core-shell nanoparticles with dox loaded.The first of topic is to study the prescription of dox and establish the dox analysis methodology.The uv absoption spectrum has 233 nm and 480 nm absoption peak,the chromatographic conditions were determined as follows:chromatography column:Diamonsil Plus C18(150 mm×4.6 mm,5 ?m);Mobile phase:acetonitrile,methanol and water(40:50:10,V/V/V);Flow rate:1.0 mL/min;Column temperature:30?;Detection wavelength of 233 nm;Sample quantity:20 ?L.The methodology results showed the uv and chromatographic method was of high accuracy and good specificity.To use thin film dispersion method to prepare liposomes.Compared with ultrasonic dispersion,high speed dispersion,ultrasonic cell crushing,high pressure homogeneous process,we found that high pressure homogeneous method was more ideal,could make the diameter of liposome is about 130 nm with uniform distribution.And temperature,speed,water bath time were studied in the process of film forming,we found the influence of these is small,and the type of phospholipids,centrifugal time,the number of homogeneous and different factors such as quality,has significant influence on it.Experiment showed HSPC,DSPC and DOPE had better drug loading than PC-98T,and the centrifugal time,number of homogeneous,and the comparison of different mass ratio with an appropriate range,the vehicle can achieve ideal result.To use CTAB template to prepare mesoporous silica.Compared the template agent of different quality,different volume of silicon source,defferent reaction time,stirring speed,reflux time and different medicine/material,we found that templateagent and silicon source should be controlled at around 0.6 g and 2.5 mL,reaction time be 1 h,stirring speed be 500 rpm and reflux time be for 24 h in a 400 mL reaction volume,at the same time,the ratio of medicine/material reached at 1:2,we found these could reach the diameter of nanoparticle is about 80 nm with uniform distribution and drug loading was about 18%.The preparation technology of hyaluronic acid modified pH-sensitive core-shell nanoparticles was based on the preparation of liposome and MSNs nanoparticles,we studied on the different quality of DOX@MSNs and different percentage of HA/Lipid,found the content of them were 15 mg and 10%,which could make the drug loading be around 8%and the PDI of nanoparticles be-37 mV.The percentage of hyaluronic acid modified core-shell nanoparticles was determined by enzyme standard instrument and the percentage were above 50%.The release studies in vitro showed that hyaluronic acid modified core-shell nanoparticle was no significant difference with no hyaluronic acid.And the pH-sensitive system maked the drug release selectively with pH and could be released in a sustained manner within 24 h,and enhanced the bioavailability of drug.The result of microplate reader showed hyaluronic acid was boned to the surface of lipid material and core-shell nanoparticle was to be active targeting carrier.Fifth,in vitro cellular uptake studies demonstrated that the core-shell system is a biomaterial without cytotoxic and the pH-sensitive delivery system targeted by hyaluronic acid with proper concentration has a better cell cytotoxic than other system. |
PDF Full Text Request