ABSTRACT
Objective To establish methods for the determination of doxorubicin and elacridar, and prepare PLGA nanoparticles for the co-delivery of doxorubicin and elacridar.Methods Ultraviolet spectrophotometry (UV) and high performance liquid chromatography (HPLC) were used to establish the determination method of doxorubicin and elacridar, respectively;co-delivery nanoparticles system was prepared by nanoprecipitation method, and optimizing the prescription was by adjusting the dosage ratio of the two drugs to investigate the particle size,morphology, encapsulation efficiency (EE), drug loading (DL) and in vitro release.Results The linearity of doxorubicin was better in the rang of 1 to 40 μg/ml, A=0.021C+0.002,r=0.999 5;the linearity of elacridar was better in the rang of 0.5 to 100 μg/ml,A=120 742.462 6C+1 974.570 4,r=1.000 0;the particle size was about 50 nm;transmission electron microscope (TEM) showed that nanoparticles were round in shape and had a good dispersion;EE of doxorubicin and elacridar were 56.58%、51.66%,respectively, DL of doxorubicin and elacridar were 1.48%、1.85%,respectively,the molar ratio of two drugs was about 1∶1;the nanoparticles released slowly in vitro.Conclusion The established methods of doxorubicin and elacridar were convenient and efficient, accurate and repeatable.The Co-delivery nanoparticles system was well dispersionand smaller size, which could be used for further studies.
ABSTRACT
OBJECTIVE: To prepare a redox and pH dual sensitive nano-carrier based on PAMAM in order to co-loading chemotherapeutics doxorubicin and breast cancer multidrug resistance reversal agent elacridar, and study their in vitro reversal effect. METHODS: The infrared spectrum FTIR was used to characterize the carrier. Confocal was used to investigate the intracellular triggered drug release. The reversal effect of breast cancer multidrug resistance and the in vitro anti-tumor activity of doxorubicin and elacridar co-loaded nanoparticles were investigated using flow cytometry and cell toxicity tests, respectively. RESULTS: The doxorubicin and elacridar co-loaded nanoparticles (PSSP/DOX/ELC) were successfully prepared, and pH-redox dual sensitive of carrier was proved by cell experiments. And the carrier was uptaken into cells and delivery to lysosome, and drug release was triggered in the lysosome acid condition, then the released drug diffused to the nucleus. The trial of rhodamine 123 accumulation and efflux assay revealed that the accumulation of rhodamine 123 was notably increased after incubation of elacridar in MCF-7/ADR cells. The cytotoxicity of PSSP/DOX/ELC nanoparticles against MCF-7/ADR cell line was significantly stronger than that of either free doxorubicin or only doxorubicin loaded nanoparticles (PSSP/DOX). CONCLUSION: The reversal effect of multidrug resistance and the cytotoxicity of cancer cells were significantly enhanced by PSSP/DOX/ELC nanoparticles. PSSP/ DOX/ELC nanoparticles is a promising delivery system.