Preparation And Pharmacodynamics Evaluation Of Zedoary Turmeric Oil Compound Liposomal Gel

Objective: To establish the best preparation process of zedoary turmeric oil compound liposomal gel(ZTOC-LG),and to investigate its in vitro transdermal properties,stability and pharmacodynamics,which provides experimental basis for further research and development of ZTOC-LG.Methods:1.Preparation and quality evaluation of zedoary turmeric oil compound liposomes(ZTOC-L): Ethanol injection method was found that is the best method to prepare the ZTOC-L in this study.The content of germacrone and tretinoin(Tre)were determined by high performance liquid chromatography(HPLC)method.Formulation process of ZTOC-L were optimized by single factor test and orthogonal test with the encapsulation efficiency and drug loading as indexes,and the particle size,Zeta potential,polymer dispersity index(PDI),morphology and stability of liposomes were evaluated.2.ZTOC-LG molding process research: Preparation of ZTOC-L by ethanol injection method,and the Carbopol-940 was added as matrix for the preparation of the ZTOC-LG.The ZTOC-LG were prepared through the single factor test and orthogonal design to optimize the prescription,in which the comprehensive score composed by forming property,glossiness,uniformity,viscosity,pH,spreadable property and stability as indexes.The stability of liposomal gel was investigated by temperature,light and humidity experiments.3.Study on in vitro transdermal properties of ZTOC-LG: Franz diffusion pool were employed to compare the permeation rate of ZTOC-LG and zedoary turmeric oil compound gel(ZTOC-G)in vitro.4.Pharmacodynamics evaluation of ZTOC-LG: The mice vaginal epithelial cell mitosis and the formation of mice tail scale epidermis model were used to compare theeffects of ZTOC-LG and ZTOC-G on the animal model of psoriasis.And the dose-effect relationship of ZTOC-LG was studied.Results:1.Preparation and quality evaluation of ZTOC-L: The optimal preparation technology were as follows: soybean phosphatidylcholine(SPC)4 mg/mL,the mass ratio of SPC to cholesterol(CH)3∶1,the mass ratio of zedoary turmeric oil(ZTO)to lipid 1∶9,the mass ratio of Tre to lipid 1∶70,the water bath temperature of 55 ℃.Encapsulation efficiencies of ZTO and Tre were(64.63 ± 1.00)% and(90.33 ± 0.72)%,respectively.Drug loading of ZTO and Tre were(9.09 ± 0.14)% and(1.43 ± 0.02)%,respectively.Particle size was(257.41 ± 7.58)nm,Zeta potential was(﹣38.77 ± 0.81)mV,PDI was0.10±0.04;the results of centrifugal acceleration test showed that the liposomes had good physical stability.No obvious change was found in each investigation index of ZTOC-L that stored at(4 ± 2)℃ for 30 d.2.ZTOC-LG molding process research: The optimal matrix prescription were carbopol 0.2 g,glycerol 3.5 g,triethanolamine 0.1 g.The experiments of stability showed that ZTOC-LG is sensitive to temperature and light but is insensitive to humidity.3.Study on in vitro transdermal properties of ZTOC-LG: In vitro transdermal experiments showed that the cumulative penetration in 24 h of germacrone and Tre in ZTOC-LG were significantly lower than ZTOC-G(P < 0.05),but the cumulative amounts in skin was significantly higher than ZTOC-G(P < 0.05).4.Pharmacodynamics evaluation of ZTOC-LG: Both ZTOC-LG and ZTOC-G could significantly inhibit the mitosis of mice vaginal epithelium(P < 0.01),and significantly promote the formation of granular layer of mice tail epidermis(P < 0.01),but the former was superior to the latter in the treatment of psoriasis.And the ZTOC-LG showed a obviously dose dependence.Conclusion: The preparation process of ZTOC-LG is simple and feasible,and the quality is controllable,and the cumulative amounts in local skin can be improved to achieve long-term sustained release,which has a good therapeutic effect on psoriasis.It hasa good prospect of application and development.