Construction of l-tetrahy-dropalmatine cubic liquid crystal gel and preliminary pharmacodynamics investigation

ZHAO Ji; ZHA Xuezhi; MEI Jiahua; TANG Junze; XUE Rui; ZHOU Yi; YANG Lijuan; MA Yunshu

doi:10.13506/j.cnki.jpr.2025.07.003

Abstract：Objective To prepare l-tetrahy-dropalmatine cubic liquid crystal gel(L-THP-CLCG)and evaluate its in vitro characteristics and preliminary pharmacodynamics.Methods A ternary phase diagram method was employed using glyceryl monooleate(GMO),anhydrous ethanol(AE),and water to preliminarily determine the optimal formulation region of L-THP-CLCG.The optimal formulation was further refined based on in vitro transdermal penetration studies.Additionally,the best penetration enhancer was selected from azone,propylene glycol,and menthol,and the skin retention profile over different time points was assessed.The preparation process was optimized using a single-factor experiment.The structure of L-THP-CLCG was characterized using polarized light microscopy,small-angle X-ray scattering(SAXS)and environmental scanning electron microscope(ESEM),while its stability and rheological properties were also evaluated.Furthermore,its analgesic effects were investigated using the hot plate test and acetic acid-induced writhing test in mice.Results The optimal formulation of L-THP-CLCG was determined as GMO∶AE∶water=63∶7∶30,with the preferred preparation process being vortexing at 60 ℃ for 3 minutes,followed by sealed storage in a 25 ℃ incubator under light protection for 24 hours.The optimal penetration enhancer was 3％ menthol,resulting in a 24-hour cumulative transdermal penetration of(1 241.39±48.83)μg·cm-2,which was significantly higher than that of the control group(P＜0.01).The skin retention study showed a gradual increase in retention from 0.5 to 10 h,reaching a maximum of(49.78±3.70)μg·cm-2 at 10 h,suggesting sustained accumulation in the skin.The obtained L-THP-CLCG was a colorless,transparent,and stable cubic liquid crystal gel with an internal double-diamond(Pn3m)lattice structure.Pharmacodynamic evaluations demonstrated that L-THP-CLCG significantly prolonged the paw-licking latency in the hot plate test and increased the pain threshold in the acetic acid-induced writhing test,reducing the number of writhes compared to the model group(P＜0.01).Conclusion The L-THP-CLCG prepared in this study exhibited a simple and stable preparation process,good transdermal penetration properties,and significant analgesic effects,providing a valuable reference for the development of transdermal delivery formulations of l-tetrahy-dropalmatine.