A Series Of Albumin-based Paclitaxel Nanoparticles: Preparation,in Vitro And In Vivo Evaluation

Paclitaxel is a classic microtubule stabilizer.It has a broad spectrum of anticancer activity due to its unique anticancer mechanism.However,its application is restricted because of its low water solubility and damage to normal tissue.The problem can be solved by the use of natural or synthetic carrier materials.The loading of paclitaxel with a carrier material can not only promote the solubility of paclitaxel,but also passively target tumor tissue.The drug resistance is currently the main reason for the reduction of the efficacy of chemotherapy drugs.Combination therapy is an effective method to reverse drug resistance.The combination of the loading of paclitaxel with a carrier material and P-glycoprotein inhibitor natural polyphenol-resveratrol with anticancer activity can successfully reverse the drug resistance of tumors.Based on the literature research and the actual situation of the laboratory,this paper studies on the preparation of different albumin nanoparticles of paclitaxel:Part ?:Firstly,the paclitaxel albumin nanoparticles with different drug loading ratios were prepared by ethanol injection method combined with high pressure homogenization.After measuring the particle size,the number of high pressure homogenization was determined to be three times.The particle size and distribution of paclitaxel albumin nanoparticles with different drug loading ratios were studied by dynamic light scattering.It was found that the particle size of albumin nanoparticle with a 9:1 ratio was the smallest.And the release of paclitaxel albumin nanoparticles with a drug loading ratio of 9:1 were the slowest.Therefore,9:1 is the optimal drug loading ratio for preparing paclitaxel albumin nanoparticles.Lastly,the stability of paclitaxel albumin nanoparticles with the drug loading ratio of 9:1 were investigated and found to be stable.Part ?:The paclitaxel-phospholipid/albumin nanoparticles were prepared by modified membrane dispersion method combined with high pressure homogenization.The optimal formulation of paclitaxel-phospholipid/albumin nanoparticles were screened by response surface,and the paclitaxel-phospholipid/albumin nanoparticles prepared by this formulation had a particle size of 117 nm.Observation by transmission electron microscopy revealed that the morphology of paclitaxel-phospholipid/albumin nanoparticles were a regular sphere.A crystallographic study of paclitaxel in nanocarriers by DSC and XRD revealed that paclitaxel was present in the nanocarriers in an amorphous form.It was found by spectroscopy that the binding of albumin to PTX-liposomes is a static quenching process.The storage stability at 4°C and the dilution stability of nanoparticles were measured by Malvern laser diffraction analyzer.It was found that paclitaxel-phospholipid/albumin nanoparticles have good stability.In vitro release experiments and pharmacokinetic experiments showed that the controlled-release of paclitaxel-phospholipid/albumin nanoparticles were more effective,and the half-life in vivo was prolonged and the plasma concentration was significantly increased,compared with paclitaxel albumin nanoparticles.And its anti-cancer activity in vitro and in vivo were stronger than albumin nanoparticles and Taxol~?.Part ?:The paclitaxel/resveratrol albumin nanoparticles were prepared by the desolvation method combined with high pressure homogenization.The optimal ratio of paclitaxel and resveratrol was 1:1.The particle size of paclitaxel/resveratrol albumin nanoparticle was 168.4 nm.After observation by transmission electron microscopy,the morphology of paclitaxel/resveratrol albumin nanoparticles were found to be a regular sphere.Crystalline study was carried out by X-ray diffraction,and it was found that paclitaxel and resveratrol were present in the nanoparticles in an amorphous form.The release of paclitaxel/resveratrol albumin nanoparticles was sequential,and resveratrol was released faster than paclitaxel.It was confirmed that the paclitaxel/resveratrol albumin nanoparticles had higher anticancer activity than single-agent nanoparticles/injection by the study of anticancer activity in vivo.