Sorafenib Nanomicelles Effectively Shrink Tumors by Vaginal Administration for Preoperative Chemotherapy of Cervical Cancer.

Jun Wang,Haini Chen,Tao Sun,Yu Liu,Fengmei Lv,Shoujin Zhao,Zhepeng Liu

doi:10.3390/nano11123271

Jun Wang, Haini Chen + Show 5 more

Open Access

https://doi.org/10.3390/nano11123271

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Abstract

To investigate the potential of sorafenib (SF) in preoperative chemotherapy for cervical cancer to reduce tumor volume, sorafenib micelles (SF micelles) with good stability and high drug loading were designed. SF micelles were prepared by film hydration followed by the ultrasonic method. The results showed that the SF micelles were spherical with an average particle size of 67.18 ± 0.66 nm (PDI 0.17 ± 0.01), a considerable drug loading of 15.9 ± 0.46% (w/w%) and satisfactory stability in buffers containing plasma or not for at least 2 days. In vitro release showed that SF was gradually released from SF micelles and almost completely released on the third day. The results of in vitro cellular intake, cytotoxicity and proliferation of cervical cancer cell TC-1 showed that SF micelles were superior to sorafenib (Free SF). For intravaginal administration, SF micelles were dispersed in HPMC (SF micelles/HPMC), showed good viscosity sustained-release profiles in vitro and exhibited extended residence in intravaginal in vivo. Compared with SF micelles dispersed in N.S. (SF micelles/N.S.), SF micelles/HPMC significantly reduced tumor size with a tumor weight inhibition rate of 73%. The results suggested that SF micelles had good potential for preoperative tumor shrinkage and improving the quality life of patients.

Highlights

SF micelles were prepared by thin-film hydration method [37], and SF micelles with different ratios of SF:TPGS were placed in small glass bottles to observe the Tyndall effect
The best ratio of SF to TPGS was further optimized by particle size, polydispersity (PDI), zeta-potential, drug loading (DL) and entrapment efficiency (EE)
It was worth mentioning that with the increased of SF from 1:40 to 4:40, the particle size did not gradually increase which might be due to the excessive TPGS forming small empty micelles, which interfere with the particle size results

Summary

Introduction

Surgery is the main treatment for early-stage cervical cancer, but for patients with intermediate and advanced cervical cancer, the opportunity for surgery is often lost

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Discussion

Conclusion