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. 2019 Dec;26(1):756-764.
doi: 10.1080/10717544.2019.1642418.

Sorafenib-loaded hydroxyethyl starch-TG100-115 micelles for the treatment of liver cancer based on synergistic treatment

Guofei Li  1 , Limei Zhao  1
Affiliations

Sorafenib-loaded hydroxyethyl starch-TG100-115 micelles for the treatment of liver cancer based on synergistic treatment

Guofei Li et al. Drug Deliv. 2019 Dec.

Abstract

Tumor microenvironment is closely related to the occurrence and development of liver cancer. Tumor-associated macrophages (TAMs) are an important part of tumor microenvironment promoting tumor deterioration and metastasis by inhibiting immune cells. Previous studies showed that PI3Kγ inhibitor could reverse the phenotype of TAMs, relieve immunosuppression and sensitize chemotherapy drugs, suggesting that the combination of PI3Kγ inhibitor and chemotherapeutics is likely to bring new breakthroughs in the treatment of liver cancer. Based on it, this paper builds HES-TG100-115-CDM-PEG micelles with tumor microenvironment responsiveness that simultaneously loaded sorafenib and TG100-115 to synergistically treat liver cancer. Pharmacokinetic study showed that the prepared micelles had longer half-life than that of the free drug solutions, which was favorable for high propensity of extravasation through tumor vascular fenestrations. Under low pH and high α-amylasereductive conditions, micelles could depolymerize quickly due to the sensitivity of bonds and enhance significantly cytotoxic activity against Hep-3B liver cancer cell. Additionally, micelles demonstrated higher levels of antitumor efficiency and better tolerance against nude mouse with Hep-3B cell than the free drug solutions. These findings reveal that HES-TG100-115-CDM-PEG micelles are a promising drug delivery system in clinical comprehensive therapy of liver cancer.

Keywords: Liver cancer; PI3Kγ; TAMs; TG100-115; micelles; sorafenib.

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Figures

Figure 1.
Figure 1.
Results of MTT assay on Hep-3B cells after incubation of 48 and 72 h with drugs solutions and micelles at various concentrations.
Figure 2.
Figure 2.
The rat plasma concentration versus time curves of micelles and drug solution after intravenous administration.
Figure 3.
Figure 3.
The tumor growth curve of nude mouse after intravenous administration of micelles and drug solutions.
Figure 4.
Figure 4.
Histology images of rat kidney tissue. (A) 100 mg/mL; (B) 500 mg/mL.
See this image and copyright information in PMC

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