This study aimed to design an effective formulation for enhancing the tumor-targeted delivery of sorafenib. Three sorafenib-loaded liposomal formulations including uncoated liposome (SF-Lip), hyaluronic acid-coated liposome (HA-SF-Lip), and PEGylated hyaluronic acid-coated liposome (PEG-HA-SF-Lip) were developed with narrow size distribution and high encapsulation efficiency. The cellular uptake and cytotoxicity of HA-SF-Lip and PEG-HA-SF-Lip were greater than those of SF-Lip in MDA-MB-231 cells overexpressing CD44, whereas there were no significant differences in MCF-7 cells with low CD44 expression, indicating the CD44-mediated cellular uptake of coated liposomes. In comparison with sorafenib solution, PEG-HA-SF-Lip increased the systemic exposure and plasma half-life in rats by 3-fold and 2-fold, respectively. Consistently, PEG-HA-SF-Lip was the most effective for tumor growth inhibition through CD44 targeting in the MDA-MB-231 tumor xenograft mouse model. Taken together, the present study suggests that PEG-HA-SF-Lip might be effective for the tumor-targeted delivery of sorafenib with enhanced systemic exposure and longer blood circulation.
|Number of pages||11|
|Journal||Nanomedicine: Nanotechnology, Biology, and Medicine|
|Publication status||Published - 2018 Feb|
Bibliographical noteFunding Information:
Funding: This research was supported by the National Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT) (No. 2016R1A2B2010097).
© 2017 Elsevier Inc.
All Science Journal Classification (ASJC) codes
- Medicine (miscellaneous)
- Molecular Medicine
- Biomedical Engineering
- Materials Science(all)
- Pharmaceutical Science