Studies on the preparation, characterization and intracellular kinetics of JD27-loaded human serum albumin nanoparticles

摘要

JD27 is a derivatives of active ingredient extracted from Rabdosia which includes a functional group of 1,2,3-Triazoles. It is considered as a promising anti-cancer drug candidate because of its low toxicity and broad-spectrum anti-cancer activity. However, the clinical application of JD27 has been limited by its poor solubility. Albumin is an attractive macromolecular carrier, which has been widely used in nanoparticle preparation. Compared with other drug delivery systems, drug-loaded albumin nanoparticles showed a series of advantages such as solubilization of hydrophobic drug, biodegradable, biocompatible and so on. In this study, JD27-loaded human serum albumin nanoparticles (JD27-NPs) were obtained using an established desolvation method and they were characterized by particle size, zeta potential, encapsulation efficiency, surface morphology and in vitro drug release studies. In addition, their cytotoxic activities, intracellular kinetics and cell membranes permeability were evaluated in EC-9706 cells. The experiment results showed that the particle size, zeta potential, and encapsulation efficiency were (276.-5±8.26) nm, (-41.4±7.21) mV and 82.2%±5.09%, respectively. SEM images suggest that JD27-NPs were a round shape, similar uniform size and smooth surface. Drug release studies indicated JD27-NPs had the properties of sustained release. The results of cytotoxic activities suggest that antitumor efficacy of JD27-NPs is higher than JD27 in EC-9706 cells. According to the results of intracellular kinetics, the concentration of JD27-NPs in the cell could reach the peak concentration after 2 hour and gradually decreases with time lasted. The AUC0-12h and MRT of JD27-NPs are significantly higher than that in JD27 (P<0.05). JD27-NPs have advantages to keep a higher and steadier intracellular concentration than JD27 which shows JD27-NPs have priority in application. The results of Hoechst 33258 staining suggested that the permeability of the cells membrane can be changed with the different concentration and treatment time of JD27. In conclusion, albumin nanopaticles may act as a useful and safe carrier for JD27.JD27-NPs will be a promising formulation for cancer therapy in future.