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.