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In Vitro Anti-tumor Efficacy Evaluation and Pharmacokinetics of Paclitaxel-Human Serum Albumin Nanoparticles

Author: DingDaWei
Tutor: HuYiQiao
School: Nanjing University
Course: Pharmacy
Keywords: Vitro potency Nanoparticles Taxol Human serum albumin Pharmacokinetics Bioequivalence Cellular uptake Plasma drug concentration Passive targeting Elimination half-life Taxol Side effects Anticancer drugs Isotonic solution Biocompatibility Tumor tissue Peak time Drug targeting Targeting Area under the curve
CLC: R96
Type: Master's thesis
Year: 2011
Downloads: 220
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Abstract

Lack of targeting in the process of cancer chemotherapy, the traditional way of administration of drugs in the body can not distinguish between normal cells and tumor cells, and the inevitable damage to normal cells while killing tumor cells, toxicity, patients treated quality of life during the decline. These lead to the application of the drug is restricted, hampered efficacy of play. Therefore, tumor targeted therapy emerged and quickly became a hot research. Human serum albumin preparation of drug-loaded nanoparticles, can significantly increase the water solubility of hydrophobic drugs, in addition to have a good biocompatibility, bio-degradable, the organisms can utilize the passive resistance and tumor targeting ability, it can also Active targeting is achieved by binding to a specific receptor on the vascular endothelial cells and tumor cell surface, while reducing the toxic side effects of antineoplastic drugs. Currently, human serum albumin as a carrier for preparation of anticancer drug delivery system has been applied in clinical. Taxol' dissertation">Taxol is a major breakthrough in the late 1990s, cancer treatment, it is one of the most effective broad-spectrum anti-cancer drug, is widely used in breast cancer, prostate cancer, ovarian cancer, head and neck cancer and non-small cell tumors treatment. However paclitaxel solubility in water is extremely small, its traditional formulation Taxol (?) Obvious side effects, aimed to reduce the toxic side effects, and improve its targeting preparations study has been a hot research field of cancer treatment. In the present study, we first use the patented process in the laboratory prepared load paclitaxel nanoparticles. Dynamic light scattering detection nanoparticle particle size of the dosage to 15% around 120nm, and the particle size uniformity. Transmission electron microscopy (TEM), scanning electron microscopy and atomic force microscopy revealed the nanoparticles appearance spherical particle size distribution in the 100-200nm between. Of this study can be measured by high performance liquid preparation of nanoparticles drug loading up to 20% or more. In addition, we found that paclitaxel albumin nanoparticles particle size, encapsulation efficiency and drug loading amount is closely related to the amount of the addition of paclitaxel. X-ray powder diffraction experiments show that the paclitaxel present in non-crystalline state in the drug-loaded nanoparticles, circular dichroism detected albumin is formed in the preparation of the nanoparticles before and after the secondary structure is almost not changed. Nanoparticles in the present study also has a very good stability. Under ambient conditions, the nanoparticles can be stably present in an isotonic solution to more than 48 hours without the occurrence of the particle size variation in the 37 ° C serum can exist stably for more than 24 hours. Measurement results in of paclitaxel an albumin nanoparticles in vitro efficacy experiments, MTT assay showed that nanoparticles of mass destruction and has been listed on preparations of MCF-7 cells with Taxol on (?) Compared with no significant sex differences, and the killing of A549 cells significantly stronger than Taxol (?) preparations in this study is able to maintain and even enhance the efficacy of paclitaxel on tumor cells. Confocal laser experiments found that nanoparticles cellular uptake and distribution in the cytoplasm, and this uptake can be a natural human serum albumin and within swallow \Flow cytometry fluorescence determination of quantitative experiments support this conclusion, the tumor cell uptake of nanoparticles through natural albumin same way, the first and the tumor cell surface receptor interactions, then may by forming the swallow \nest \Finally, PTX-HSA nanoparticles in cynomolgus monkeys in vivo pharmacokinetic experiments showed that two formulations of the plasma concentration-time curve is very similar, and the area under the peak time, peak concentration, curve and elimination half-life indicators no significant differences in resistance. These fully proved PTX-HSA nanoparticles and listing agents bioequivalence, showing good prospects for the clinical application of this study preparations.

In Vitro Anti-tumor Efficacy Evaluation and Pharmacokinetics of Paclitaxel-Human Serum Albumin Nanoparticles

Abstract

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