Preparation Characterization And Evaluation Of In Vitro Antitumor Activities Of Folate-conjugated Docetaxel-loaded Bovine Serum Albumin Tumor-targeting Nanoparticles

Docetaxel (DT), produced on the basis of paclitaxel, is the representative among the second generation of taxane anticancer drugs. In anti-cancer experiments, the activity of docetaxel is higher than that of paclitaxel. This kind of drug has a good effect not only on ovarian cancer, non-small cell lung cancer and breast cancer, but also on prostate cancer, pancreatic cancer, and multiple soft tissue tumors. Therefore this drug is currently the first-line drug in_clinical chemotherapy. But in the current preparations of docetaxel, there are still some drawbacks such as water-insolubility, non-targeting ability, sensitization and toxic side effects.Focusing on its drawbacks of low water-solubility and non-targeting ability, the author in this paper makes a study of targeting water-soluble preparations, trying different methods to prepare docetaxel nanoparticles such as the conventional anti-solvent method, mechanical crushing method, ultrasonic emulsification method and supercritical fluid anti-solvent method. However, due to the limitations of their own the author can not get the satisfactory nano-drugs. The final choice of desolvation-chemical crosslinking method to prepare DT-BSA-NPs helps to solve the problem of docetaxel's water-solubility, and the use of folate coupling with DT-BSA-NPs helps to solve the problem of its non-targeting ability.Through testing the important factors during preparation, selecting the feasible range of six factors, and using the software Design-expert for data optimization, the author analyses important conditions in the experiments such as the concentration of BSA, the concentration of DT, the ratio of ethanol and water, the cross-link ratio, the dripping speed and so on. The final optimal conditions are as follows:the concentration of BSA is 35.1 mg/mL, the concentration of DT is 3.96 mg/mL, the ratio of ethanol and water is 2.99, the dripping speed of ethanol is 0.5 mL/min, the stirring time is 36 h, and cross-link ratio of glutaraldehyde and BSA is 1. According to these conditions, the expected results are:the particle size of BSA microspheres is 181.65nm, the maximal entrapment rate is 26.3% and the maximal drug-loading rate is 12.43%.Through certification test, DT-BSA-NPs are measured by laser particle analyzer for the size and potential, to obtain the data that the particle size of DT-BSA-NPs is 188nm and their potential is -39.76mV. Measured by ultraviolet spectrophotometer, the entrapment rate is 30.63 % and their drug-loading rate is 13.92%. These data confirm that products meet the requirements.And then the author makes a preparation of folate active ester coupling with DT-BSA-NPs to get FA-DT-BSA-NPs, letting the drug have targeting ability. He tests FA-DT-BSA-NPs by ultraviolet spectrophotometer to obtain the ratio of mole of BSA/mole of coupling folate as 1:...