Study on different particle sizes of DOX-loaded mixed micelles for cancer therapy.

Nano-based drug delivery systems have been widely applied in cancer therapy, among that, particle sizes may affect the delivery efficiency of nanocarriers. The purpose of this study was to evaluate the potential impacts of particle size on tumor therapy, in consideration of this, lipid/glycocholic acid mixed micelles (LGs) were designed as the model nanocarriers. Doxorubicin (DOX) loaded LGs with two different particle sizes at around 10 nm and 100 nm, respectively, were successfully prepared by controlling the ratio of EPC to GAH. In vitro release study showed that the release behaviors of DOX in mixed micelles with two different particle sizes was basically consistent and showed sustained release. DOX-LGs at 10 nm exhibited higher cellular uptake capacity, compared with DOX-LGs at 100 nm. Besides, in vivo NIFR imaging also demonstrated that DOX-LGs at 10 nm had more accumulation in tumor site. Furthermore, DOX-LGs at 10 nm presented both higher in vitro cytotoxicity and superior in vivo antitumor activity than that of 100 nm. In vivo safety evaluations showed that the mixed micelles had lower toxicities than free DOX solution formulations. These results indicated that the nanoparticles with smaller particle size could improve the profiles in cellular uptake, tumor accumulation as well as anti-tumor efficacy, which would provide a theoretical principle for the design of nanoparticles.