1.Construction of Saikosaponin D Multifunctional Liposomes and Evaluation of Its Anti-liver Cancer Efficacy and Targeting
Kun YU ; Guochun YANG ; Yaliang JIANG ; Yunting XIAO ; Congxian WANG ; Qionge SUN ; Ziyue LI ; Yikun SHANG ; Yu MAO ; Xin CHENG
Chinese Journal of Experimental Traditional Medical Formulae 2026;32(9):205-216
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.
2.Neuroimaging study of interlaminar percutaneous endoscopic lumbar discectomy
Yanhong LIU ; Bo ZHONG ; Shengtao WANG ; Congxian YANG ; Siyan ZHANG ; Sanliang LI ; Huayong CHEN
Chinese Journal of Neuromedicine 2019;18(8):818-823
Objective To utilize the magnetic resonance neurography (MRN) as a feasible tool for measuring the anatomical parameters of lumbar spinal nerves, and further to evaluate the neuro-safety of interlaminar percutaneous endoscopic lumbar discectomy.Methods Thirty healthy adult volunteers without significant history of low back pain or lumbar deformity were selected in our hospital from September 2016 to December 2016. All subjects accepted MRN. The nerve roots of L2-S1 were measured at the starting point of dural sac, and the angles between nerve roots and dural sac were measured. The distances between L2-L5 nerve roots and the edge of ipsilateral dural sac were measured and analyzed statistically.Results All MRN showed a gradual increase in the origin of the nerve roots from L2 to S1. The origin of the root was found to be below the corresponding disc for the L2 to L4 roots. There were 70% of the L5 roots originated below the L4/5 disc, 26.7% at the L4/5 disc, and 3.3% above the L4/5 disc; about 70% of the S1 roots originated above the L5/S1 disc. There were no statistically significant differences in the angles between dural sac and both left and right nerve roots (P>0.05). The angels between the nerve root and the dural sac from L5 and S1 was smaller than those from L2, L3, and L4 (P<0.05); that from S1 was significantly smaller than that from L5 (P<0.05). The distance of the nerve root and the ipsilateral dural sac was significantly increased in each side from L2 to L5 (P<0.05). There was no statistically significant difference in the distances between the left and right nerve roots and the edge of the ipsilateral dural sac in the same segment (P>0.05).Conclusion MRN is a feasible tool to measure the anatomical parameters of the lumbar spinal nerve, and there is a safe neurological area of the percutaneous endoscopic lumbar discectomy through the interlaminar approach.
3.The effect of Resolvin D1 on the radicular pain induced by herniated nucleus pulposus
Zhihua LIU ; Ling ZUO ; Guishen MIAO ; Junnan WANG ; Congxian YANG ; Zhijian FU ; Tao SUN
Chinese Journal of Physical Medicine and Rehabilitation 2016;38(11):819-824
Objective To investigate the analgesic effect of Resolvin D1 (RvD1) on radicular pain induced by herniated nucleus pulposusand its underlying mechanism.Methods Fifty-six male rats were randomly divided intoa sham group,a model group,a 10 ng group anda 100 ng group,each of 14.The rat model of non-compressive lumber disc herniation was established in all except the sham group.The former two groups were then injected with 10 μl of phosphate buffer solution (PBS) while the latter 2 groups were injected with 10 μl of PBS containing 10 and 100 ng of RvD1 respectively daily for three successive days.The rats' 50% paw withdrawal threshold (PWT) was evaluated 1 day before and on 7 successive days after surgery.On day 7 the rats' spinal cords were removed to assess the expression of tumor necrosis factor-or (TNF-α),interlukin-1β (IL-1β) and interlukin-10 (IL-10) using ELISA methods.The levels of ERK and NF-κB/p65 were measured using Western blotting.Results Theaverage 50%PWT of the model group decreased significantly from day 1 to day 7 compared with the sham group,but was significantly lower thanthe RvD1 10 ng group from day 3 to day 7.Moreover the 50%PWT in the RvD1 100 ng group increased significantlyfrom day 2 to day 7 compared with the model group (P<0.05).The average expression of both TNF-α and IL-1β of the model group was upregulated significantly and that of IL-10 decreased significantly compared with the sham group.Compared with the model group,the expression of TNF-α and IL-1β decreased significantly (P<0.05)and the level of IL-10 was significantlyup-regulated (P<0.05) both in the RvD1 10 ng group and 100 ng group.Moreover,the changes were larger in the RvD1 100 ng group (P<0.05).Compared with the sham group,the levels of p-ERK and NF-κB/p65 in the model group were significantly up-regulated (P<0.05).Compared with the model group,intrathecal injection of RvD1 (10 ng or 100 ng) significantly decreased the expressions of p-ERK and NF-κB/p65 (P<0.05).Moreover,the decrease wasgreater in the RvD1 100 ng group (P<0.05).Conclusions RvD1 might alleviate the radicular inflammation and pain byregulating the balance of inflammatory mediators and activation of p-ERK and NF-κB/p65 pathways.It may offer novel therapeutic approaches for the management of lumbar disc herniation.

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