The Study Of Paclitaxel Vitamin E TPGS-L-polylactic Copolymer Nanoparticles

Vitamin E polyethylene glycol 1000 succinate-L-polylatic copolymer whith hydrophilic and hydrophobic segments can be used as nanoparticles carrier, and Copolymer degradation product-Vitamin E succinate has a certain anti-cancer activity, very suitable for anti-cancer drug carrier.The different TPGS-PLLA copolymers were synthesized by bulk ring-opening polymerization of L-lactide (L-LA) using Stannous octoate (Sn (Oct)2) as catalyst. The relative molecular weight, structure and properties of TPGS-PLA were systematically characterized with GPC, FTIR,1H NMR, DSC. The study found that when the 13%TPGS content has the maximum intrinsic viscosity [η]=18.659 cm3·g-1, the copolymer molecular weight is Mn= 6907. Hydrophilic study showed TPGS as segment content increased, large water absorption. The degradatione study have proved as the smaller PLLA copolymers, and more fast the degradation of copolymer.PTX TPGS-PLLA nanoparticles were prepared through solvent evaporation method, and their influencing factors were studied. The encapsulation efficiency, Drug loading concent and diameters were as indicators and single factor and Orthogonal design were used to get a better quality preparation of nanoparticles, particle size of nanoparticles is 196.4±41.3nm, drug loading 8.37%±0.03, encapsulation efficiency above 90%. The in vitro release results show that the nanoparticles vector is slow-release paclitaxel. Paclitaxel TPGS-PLLA nanoparticles released about 60～70% drug within 15 days, and the release is fit with the Higuchi equation y= 14.534t1/2 +12.641. Stability studies showed that freeze-dried powder should be avoided in high-temperature, high humidity and light conditions conservation and is proposed to preserve in confined conditions.Hemolytic experiments showed the nanoparticles were not hemolytic, and suitable for intravenous administration. MTT method through comparison of drug-loaded nanoparticles and paclitaxel for non-small cell lung cancer cell inhibition, the results showed that:The results showed that paclitaxel TPGS-PLLA nanoparticles for non-small cell lung cancer cells inhibited the rate of inhibition with time-dependent manner, with the extension of time drug, the more obvious role.Plasma and various tissues at different time points the concentration of paclitaxel was determined in rats after tail vein injection by HPLC method. Compared pharmacokinetics and tissue distributions with paclitaxel injection and paclitaxel nanoparticles in mice, The results showed that paclitaxel nanoparticles was rapidly distributed into the liver, spleen and lung tissues. The AUC is increased in the liver, spleen and lung and is 18.91,26.92 and 6.72-fold of Paclitaxel injection.Therefore, there might be decreased chances of the toxicity in blood. It indicated that paclitaxel TPGS-PLLA nanoparticles could improve drug targeting.