Na Qu, Yating Sun, Jing Xie, Lesheng Teng1. 1. College of Life Sciences, Jilin University, No.2699, Qianjin Street, Changchun, 130012. China.
Abstract
BACKGROUND: A novel formulation for cabazitaxel loaded HSA nanoparticle (Cbz-NPs) with non-crosslinking agent participation was reported in this study. OBJECTIVE: A simple method through unfolding of HSA self-assembling nanoparticle for cabazitaxel (Cbz) overcomes the drawbacks of Cbz with high toxicity, poor solubility and low tissue specificity, and avoids side effects of polysorbate 80 which is commonly used for dissolving Cbz. METHOD: The optimum condition was obtained by Response surface methodology (RSM). The NPs were analyzed by differential scanning calorimetry (DSC) and drug release in vitro was also determined. Furthermore, cytotoxicity, cellular uptake were assessed. RESULTS: The experimental encapsulation efficacy (EE) is 52.95%, which is close to the predicted value of 62.44%, indicating the correct prediction, and the nanoscale-sized particles enhanced permeability and retention (EPR) effect. Differential scanning calorimetry (DSC) demonstrates an amorphous state of cabazitaxel-NPs, and a sustained release was found in vitro drug release. Human prostate cancer lines PC3 and Human Lung Cancer line A549 were employed for cytotoxicity study by the MTT test. Single solvent with polysorbate 80 showed serious cytotoxicity with the cell viability of only 80% while no toxicity was found in drug-free nanoparticles. Fluorescence intensity of FITC-HSA nanoparticles encapsulating Cbz increased with the incubation time. The cellular localizatiton of cabazitaxel-NPs was observed by confocal microscopy. CONCLUSION: Cbz-NPs may be considered as a viable opportunity for anticancer drug delivery.
BACKGROUND: A novel formulation for cabazitaxel loaded HSA nanoparticle (Cbz-NPs) with non-crosslinking agent participation was reported in this study. OBJECTIVE: A simple method through unfolding of HSA self-assembling nanoparticle for cabazitaxel (Cbz) overcomes the drawbacks of Cbz with high toxicity, poor solubility and low tissue specificity, and avoids side effects of polysorbate 80 which is commonly used for dissolving Cbz. METHOD: The optimum condition was obtained by Response surface methodology (RSM). The NPs were analyzed by differential scanning calorimetry (DSC) and drug release in vitro was also determined. Furthermore, cytotoxicity, cellular uptake were assessed. RESULTS: The experimental encapsulation efficacy (EE) is 52.95%, which is close to the predicted value of 62.44%, indicating the correct prediction, and the nanoscale-sized particles enhanced permeability and retention (EPR) effect. Differential scanning calorimetry (DSC) demonstrates an amorphous state of cabazitaxel-NPs, and a sustained release was found in vitro drug release. Humanprostate cancer lines PC3 and Human Lung Cancer line A549 were employed for cytotoxicity study by the MTT test. Single solvent with polysorbate 80 showed serious cytotoxicity with the cell viability of only 80% while no toxicity was found in drug-free nanoparticles. Fluorescence intensity of FITC-HSA nanoparticles encapsulating Cbz increased with the incubation time. The cellular localizatiton of cabazitaxel-NPs was observed by confocal microscopy. CONCLUSION:Cbz-NPs may be considered as a viable opportunity for anticancer drug delivery.