Sorafenib-Loaded Polymeric Micelles As Passive Targeting Therapeutic Agents for Hepatocellular Carcinoma Therapy

Abstract

Aim: The clinical application of sorafenib is limited because of its hydrophobicity, low bioavailability and unsatisfying treatment effect. Therefore, sorafenib-loaded PEG-poly (ε-caprolactone) micelles (SF micelles) were fabricated for sorafenib delivery. Materials & methods:In vitro assays investigated the solubility, dispersity, stability, cytotoxicity and uptake capacity of SF micelles. In vivo biodistribution and therapeutic effects were studied using HepG2-Luc tumor-bearing mice. Results: SF micelles had a regular spherical structure with good water solubility. In vivo imaging results showed PEG-poly (ε-caprolactone) micelles could elevate the sorafenib concentration in tumor tissues. Meanwhile, SF micelles exhibited higher tumor growth inhibition in vivo. Conclusion: SF micelles might be a potential drug delivery system, which could enhance the therapeutic effects of sorafenib.

Keywords:

• drug delivery
• hepatocellular carcinoma
• micelles
• sorafenib
• therapy

Supplementary data

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Authors’ contributions

Each co-author listed above participated sufficiently in the work to take responsibility for the content, and that all those who qualify are listed. Authorship credit should be based on: substantial contributions to the conception or design of the work, or the acquisition, analysis or interpretation of data for the work; drafting the work or revising it critically for important intellectual content; final approval of the version to be published; and agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. In addition to the listed co-authors, M Zhan contributed to the experimental design. W Shang and S Fu assisted with revising the work critically for important intellectual content.

Financial & competing interests disclosure

This study is supported by the National Key Research and Development Program of China under Grant number 2017YFA0205200, 2016YFC0103702 and 2016YFA0201401, the National Natural Science Foundation of China under Grant number 81571785, 81771957, 81227901, 61231004, 61671449, 21604025, 51273072 and 81701771, the Natural Science Foundation of Guangdong Province, China under Grant number 2016A030311055, 2016A030313770, 2014B090907004 and 2016A030310461, Science and Technology Foundation of Guangdong Province, China under Grant number 2013B021800180. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical disclosure

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.