Construction of Saikosaponin D Multifunctional Liposomes and Evaluation of Its Anti-liver Cancer Efficacy and Targeting
10.13422/j.cnki.syfjx.20252162
- VernacularTitle:柴胡皂苷D多功能脂质体的构建及其抗肝癌功效与靶向性评价
- Author:
Kun YU
1
;
Guochun YANG
1
;
Yaliang JIANG
2
;
Yunting XIAO
1
;
Congxian WANG
1
;
Qionge SUN
1
;
Ziyue LI
1
;
Yikun SHANG
1
;
Yu MAO
1
;
Xin CHENG
1
Author Information
1. School of Chinese Materia Medica，Yunnan Provincial Key Laboratory of Research on External Drug Delivery System and Preparation Technology in Universities，Yunnan Key Laboratory of Dai and Yi Medicines，School of Basic Medical Sciences，Yunnan Key Laboratory of Chronic Disease Prevention and Treatment of Integrated Traditional Chinese and Western Medicine，Yunnan University of Chinese Medicine，Kunming 650500，China
2. Kunming Zhongkang Pharmaceutical Co. Ltd.，Kunming 650601，China
- Publication Type:Journal Article
- Keywords:
saikosaponin D;
multifunctional liposomes;
poloxamer 407;
curcumin;
subcutaneous solid tumor;
small animal in vivo imaging
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(9):205-216
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo construct a multifunctional liposomal delivery system by replacing cholesterol（Chol） in conventional liposomes with saikosaponin D（SSD） and modifying with poloxamer 407（P407） for co-delivery of curcumin（Cur）. The system was evaluated for in vivo tumor targeting and inhibitory effects on mouse subcutaneous solid tumors. MethodsSingle-factor and orthogonal tests combined with information entropy weighting were used to optimize the formulation process of the liposome with encapsulation efficiency and absolute Zeta potential as indexes， and validation studies and liposomal characterization were performed. A subcutaneous solid tumor model was established by injecting H22 hepatocellular carcinoma cells subcutaneously into the dorsal surface of the right forelimb of mice. DiR-loaded traditional Chol liposomes（P407-DiR-Chol-LPs， PDCL） and novel SSD-based liposomes（P407-DiR-SSD-LPs， PDSL） were prepared by the optimized formulation process， and tail vein injection was performed to investigate the impact of SSD on liposome tumor targeting with small animal in vivo imaging. Mice were randomly divided into eight groups， including blank group， model group， free doxorubicin（DOX） group（2 mg·kg-1）， free Cur group（8 mg·kg-1）， free SSD group（10 mg·kg-1）， P407-Cur-Chol-LPs（PCCL） group， P407-SSD-LPs（PSL） group， and P407-Cur-SSD-Lps（PCSL） group. Treatments were administered intraperitoneally every other day for seven doses. Antitumor efficacy and biocompatibility were evaluated by monitoring body weight change， organ indices， tumor volume and mass， relative tumor proliferation rate（T/C）， and tumor growth inhibition rate（TGI）. Histopathological analysis of liver， kidney， and tumor tissues was performed using hematoxylin-eosin（HE） staining. Serum levels of aspartate aminotransferase（AST）， alanine aminotransferase （ALT）， blood urea nitrogen（BUN）， and creatinine（Crea）in mice were quantified by fully automated biochemical analyzer. ResultsOrthogonal test yielded optimal ratios of Cur， SSD， and P407 to soybean phosphatidylcholine（SPC） as 1∶25， 1∶20， and 1∶4. The optimized PCSL exhibited spherical morphology with a particle size of 179.15 nm， a Zeta potential of -47.25 mV， and an encapsulation efficiency of 96.40%. Its in vitro release profile conformed to first-order kinetics， demonstrating excellent storage stability and hemocompatibility. In vivo imaging revealed that the fluorescence signal in tumor tissues and the fluorescence intensity ratio between tumors and organs were significantly higher in the PDSL group than in the PDCL group（P<0.05， P<0.01）. Among the treatment groups， PCSL group showed superior efficacy over free Cur group， free SSD group， PCCL group， and PSL group， with TGI>40% and T/C<60%， indicating pronounced anti-hepatocellular carcinoma effects（P<0.05， P<0.01）. Histopathology and serum biochemistry indicated minimal hepatorenal toxicity and improved hepatic and renal function in PCSL-treated mice. ConclusionReplacing Chol with SSD in preparing multifunctional drug delivery systems not only stabilizes liposomes but also yields superior anti-hepatocellular carcinoma efficacy， achieving the effect of drug-excipient integration. Co-delivery of Cur via this system can be used for treating subcutaneous solid tumors in hepatocellular carcinoma， providing new insights and technical approaches for anti-hepatocellular carcinoma research and the meridian-guiding and messenger-directing theory in traditional Chinese medicine.
