Preparation, in vitro anti-tumour activity and in vivo pharmacokinetics of RGD-decorated liposomes loaded with shikonin

Abstract

Shikonin (SHK) has been evidenced to possess effects against various cancer cells. However, poor aqueous solubility and high toxicity restrict its application. In the study, RGD-decorated liposomes loaded with SHK (RGD-Lipo-SHK) were prepared via thin-film hydration method. Characterization and cellular uptake of liposomes was evaluated. Cytotoxicity of blank liposomes and different SHK formulations was measured against breast cancer cells (MDA-MB-231, MCF-7, and MCF-10A). Anti-tumour effects and pharmacokinetic parameters of different SHK formulations were appraised in tumour spheroids and in rat model, respectively. Liposomes displayed a particle size of less than 127 nm with a polydispersity index about 0.21. The encapsulation efficiency was about 91% for SHK, and drug leakage rate of liposomes was less than 6%. RGD-Lipo-SHK showed superior cellular internalization in the α_vβ₃-positive MDA-MB-231 cells. Blank liposomes had no cytotoxicity to MDA-MB-231 and MCF-7 cells. Howbeit, different SHK formulations obviously inhibited proliferation of MCF-10A cells, especially free SHK. Meanwhile, RGD-Lipo-SHK significantly inhibited growth inhibition of tumour spheroids. The pharmacokinetics study indicated that the peak concentration, area under plasma concentration-time curves, half-life, and mean residence time of RGD-Lipo-SHK distinctly increased compared with those of free SHK. Altogether, these results demonstrated RGD-Lipo-SHK could reduce cytotoxicity, strengthen the antitumor-targeted effect, and prolong circulation time, which provides a foundation for further in vivo experimentations.

Keywords:

• Shikonin
• liposomes
• tumour spheroids
• pharmacokinetics
• breast cancer

View correction statement:

Correction

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This study was approved by Heilongjiang Provincial Natural Science Foundation of China (No. LH2019H065), Scientific Research Fundation of Heilongjiang Provincial Education Department (No. 2019-KYYWF-1257), and Young Doctor Fundation of Qiqihar Academy of Medical Sciences (No. QMSI2020B-05).