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Formula optimization and in vivo study of poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/combretastatin A4/BLZ945 nanoparticles for cancer therapy.
International Journal of Pharmaceutics 2023 March 17
Poly(L-glutamic acid)-g-methoxy poly(ethylene glycol)/Combretastatin A4 (CA4)/BLZ945 nanoparticles (CB-NPs) have shown great potential in synergistic cancer therapy. However, it is still unclear how the nanoparticles' formula, such as injection dose, active agent ratio, and drug loading content, affects the side effects and in vivo efficacy of CB-NPs. In this study, a series of CB-NPs with different BLZ945/CA4 (B/C) ratios and drug loading contents were synthesized and evaluated on a hepatoma (H22) tumor-bearing mice model. The injection dose and B/C ratio were found to have a significant influence on the in vivo anticancer efficacy. The CB-NPs 20 with B/C weight ratio of 0.45/1, and total drug loading content (B + C) of 20.7 wt%, showed the highest potential for clinical application. Systematic pharmacokinetics, biodistribution, and in vivo efficacy evaluation for CB-NPs 20 have been finished, which may provide significant instruction for medicine screening and clinical application.
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