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  • Title: Impacts of particle size on the cytotoxicity, cellular internalization, pharmacokinetics and biodistribution of betulinic acid nanosuspensions in combined chemotherapy.
    Author: Wang R, Wang X, Jia X, Wang H, Li W, Li J.
    Journal: Int J Pharm; 2020 Oct 15; 588():119799. PubMed ID: 32828973.
    Abstract:
    To evaluate the effect of particle size on the cellular internalization, tissue distribution, and bioavailability of betulinic acid nanosuspensions (BA/NSs) and further investigate the combined effect of BA/NSs and Taxol® on breast cancer, BA/NSs with different particle sizes (160 nm, 400 nm, and 700 nm) were prepared by an efficient universal green technology. The use of BA/NS (160 nm) was more likely to increase the BA release rate and enhance bioavailability compared with the use of larger size particles. BA/NSs were internalized by 4T1 cells in different ways, including clathrin-mediated endocytosis, caveolae-mediated endocytosis, and macropinocytosis. For the 4T1 orthotopic tumor model, BA/NS (160 nm) showed a tendency to accumulate at a higher level in tumor tissue. Moreover, combination therapy with BA/NSs and Taxol® showed remarkable potential to enhance antitumor activity in vitro and in vivo. The cytotoxicity and apoptotic ability of the different preparations decreased in the following order: BA/NS (160 nm) + Taxol®, BA/NS (400 nm) + Taxol®, and BA/NS (700 nm) + Taxol®. The tumor inhibition rates of BA/NSs (160 nm, 400 nm, and 700 nm) combined with Taxol® were 2.35-, 1.74- and 1.12-fold higher than that of free BA, respectively. The combined chemotherapy showed good safety, indicating that it had the effect of enhancing treatment and reducing toxicity.
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