The Study Of Solid Lipid Nanoparticles Composite With Single-walled Carbon Nanotube And Docetaxel

Docetaxel (DTX) is a new generation taxane anticancer drug，which has beenlisted. And it can destroy tumor cells in mitosis. But DTX has poor solubility in water,so Tween80and ethanol are added in the prescription of Taxotere@, which can causea variety of adverse reactions such as allergic reactions, dermatitis, and fluid retention.SWNT has lots of unique physical, chemical and biological properties, making thisnano-material attractive for biomedical applications, including bio-sensordevelopment, bio-electro-chemistry, biomedical devices, deliveries of biomedicalcargoes (including drugs, genes, proteins etc.) into cells because of its unique size andhollow structure. Solid lipid nanoparticle (SLN) has a series of advantages, includegood physiological compatibility, a suitable delivery for a liposoluble drug, atargeting drug delivery system with its surface modification, etc. Therefore, SLN hasbeen reported as a promising anticancer drug delivery system.In this paper, we obtained ultra-short oxidized SWNT (OSWNT) using mixedacid oxidation method. We intend to improve its water dispersion ability and reduceits toxicity. Then, DTX is conjugated with OSWNT via π-π stacking interaction. Adrug delivery system DTX/OSWNT/SLN was prepared following a micro-emulsiontechnique. We evaluate its antitumor activity in vitro by SRB assay against humanbreast cancer cells (MCF-7cells).Firstly, the water-solvable ability of SWNT was modified to a certain extent,which is much easier to load with drugs. We prepared DTX/OSWNT/SLN by meltultrasonic dispersion method. The SLN was formulated with glyceryl monostearate，phospholipids and polxamer188as emulsifiers. This paper makes the finalprescription with single factor experimental design orthogonal experimental design.Transmission electron microscopy (TEM) was employed to study the shape ofDTX/OSWNT/SLN. Ultra-filtration centrifugation method was applied to separatefree DTX and DTX/OSWNT/SLN. The drug concentration was then determined byHPLC method. The drug release behavior in vitro was studied by dialysis method.The morphology of DTX/OSWNT/SLN was approximately spherical，the particle size and zeta potential were（181.3±3.23）nm and（-33.65±1.28） mV, respectively.The entrapment efficiency and drug loading of DTX/OSWNT/SLN was (96.43±0.97)%and（8.51±0.08）%, respectively. The results showed that the drug releasefrom DTX/OSWNT/SLN was slower than DTX and fitted well with Weibullequation.The anti-tumor activity of DTX/OSWNT/SLN was tested by SRB assay againstMCF-7cells．FITC was combined with DTX/OSWNT/SLN in order to evaluate theuptake of MCF-7cells in vitro．The results showed that DTX/OSWNT/SLN maytransfer into the cell through the membrane of MCF-7cells in4h,DTX/OSWNT/SLN revealed more cytotoxicity against MCF-7cells by inducingmore apoptosis and more G2/M inhibition compared with DTX.In summary, this paper successfully prepared a drug delivery systemDTX/OSWNT/SLN. Its physical-chemical properties and anti-tumor activity in vitrowere investigated. The experiment results preliminary indicated that the nanoparticlesmay be a promising anti-tumor targeting drug delivery system.