| ObjectiveIn this study,the basic physical and chemical properties of baicalin,balanced solubility,selection of liposome preparation methods,and compatibility of raw materials and excipients were firstly determined by pre-prescription research to determine the preparation of baicalin liposomes.Then the formulation process of baicalin liposomes was optimized,and the baicalin liposome gel was prepared and the preliminary quality evaluation was carried out.On the basis of the preparation,further investigation of the acne pharmacodynamics test is carried out,which provides a certain reference for the development of baicalin transdermal preparations.Method1.The preliminary stability and equilibrium solubility of baicalin in different phosphate buffer media at 32℃were investigated,and the compatibility of raw materials and excipients were investigated to lay the foundation for the subsequent selection of liposome preparation methods and selection of hydration solutions.2.In the preparation process of baicalin liposomes,a single factor test was used,and the encapsulation efficiency and particle size were used as evaluation indicators to investigate the influence of the formulation process on the preparation of liposomes.The correlation between each factor and the encapsulation efficiency was used to select the significant factors affecting the preparation of liposomes,and then the Box-Behnken response surface method was used to further optimize the formulation.On this basis,the preparation process of baicalin liposomes was determined.3.Preliminarily screen the blank matrix of the gel through related experiments,and determine the baicalin liposome gel by means of viscosity test,rheology test,establishment of high-performance liquid content determination method for liposome gel,etc.The rheology,in vitro release and in vitro transdermal penetration of the baicalin liposome gel were investigated from various aspects.4.The appearance of baicalin liposomes,the p H value,the particle size distribution of baicalin liposomes in the gel,and the preliminary stability test were used to investigate the preliminary quality of the preparation.5.Established a rabbit ear acne model,and judge whether the model is successful or not through the appearance index and H&E staining.Then H&E staining was performed on the rabbit ear acne model after administration.At the same time,TNF-α,IL-1β,IL-6,and IL-8 in the rabbit ear acne model serum before and after administration were used as detection indicators to explore the baicalin liposomes.The inhibitory effect of the gel on the level of inflammatory factors in the rabbit ear acne model.Result1.The stability and solubility of baicalin in the phosphate buffer under different p H conditions showed that the solubility of baicalin in the phosphate buffer at p H=7.4reached(6451.90±62.58)μg/m L,and the baicalin The glycoside is stable,and the phosphate buffer with p H=7.4 is selected as the hydration solution for liposome preparation.In the preparation method,the screening film dispersion method is used as the preparation method of baicalin liposomes.The results of the compatibility test of the raw materials and excipients showed that the related substances produced did not increase significantly,and the selected excipients can be used for later prescription screening.2.After single factor investigation of baicalin liposomes and optimization of star-point response surface methodology,the optimal liposome preparation and formulation process conditions are as follows:(1)Precisely weigh 15 mg of baicalin crude drug,add it to 3m L of PBS buffer(p H=7.4)to dissolve it and place it at 40°C for incubation until use;(2)Weigh 100 mg of soybean lecithin,30mg of cholesterol,and 1 mg of vitamin E.Pipette 8 m L of chloroform and 4 m L of methanol into an eggplant-shaped bottle.Ultrasound for 10 minutes to dissolve the lipid components in the chloroform/methanol mixture;(3)Put the lipid solution of(2)above on a rotary evaporator,set the temperature of the water bath to 32℃,and rotate the steam at 55 rpm,and then steam to form a uniform lipid film in the eggplant-shaped bottle;(4)Put the PBS buffer solution of(1)dissolving baicalin into the lipid film formed in(3)above,put it in a 40℃water bath,add 20μL Tween 80 dropwise,keep it for 3hours,and keep it warm.Shake properly to make the hydration liquid come into contact with the lipid film sufficiently,then place it on a rotary evaporator,and hydrate it for 47minutes at 40℃and 40 rpm to obtain a light yellow suspension.(5)The pale yellow suspension formed in(4)was refrigerated for 30 minutes,and then probed ultrasonically,probed with a superpower of 60 W,3-3 s,for 6 minutes,and then filtered through a 0.45μm and 0.22μm microporous membrane for 3 times.The granule is sized to reduce the particle size,and the baicalin liposome is prepared and placed in the refrigerator for use.The appearance of the prepared liposomes was found to be quasi-spherical,with complete structure and uniform dispersion,with a particle size of about 200nm,a PDI polydispersity index of 0.217,and a Zeta potential of-32.4m V.Liposomes of baicalin are stored at 4℃,the leakage rate of liposomes is low,and the stability is good.3.The successfully prepared baicalin liposome gel had a uniform content,and the prepared baicalin liposome gel is a pseudoplastic fluid.Three batches of liposome gel prepared according to the same process were used for rheology.The test results show that the rheological properties of the gel are stable.The release of the dialysis bag showed that the in vitro release performance was good,and it showed a sustained release effect.In the in vitro transdermal release test,the cumulative permeation of baicalin liposome gel can reach(81.38±2.81)μg/cm~2per unit area in 18 h,and the permeation law in vitro conforms to the first-order equation.It is used to treat acne propionic acid.Acne caused by inflammation caused by bacilli provides the basis for the preparation.4.The liposome gel prepared in this experiment found through its preliminary quality research that the baicalin liposome gel has a pale yellow appearance,good uniformity,fineness,moderate viscosity,and p H=6.42±0.13.In addition,the liposomes are well dispersed in the carbomer gel and can be evenly distributed in the gel,without agglomerates and liposomes with larger particle size.The liposomes were stored at room temperature and 4℃,and liposome gels were stored at 4℃under refrigeration,high humidity and light for 30 days.It was found that liposomes and liposome gels were both stored at 4℃The cold storage is most stable under the conditions,the particle size,PDI and encapsulation efficiency of liposomes do not change significantly,and the appearance properties,viscosity and content of the gel do not change significantly.5.After oleic acid blocked the rabbit ear hair follicles,and 15 days after applying Propionibacterium acnes to make the model,the apparent and pathological indexes of the acne model showed that the model was successful.After 21 days of administration,the effect of liposome gel group was observed from the results of histopathological staining,which was mainly reflected in reducing the degree of keratinization,local tissue congestion,and the degree of inflammation.After administration and treatment,the effects of the secretion of TNF-α,IL-1β,IL-6,and IL-8 in the serum of rabbit ear acne model found that baicalin liposome gel can significantly reduce the level of inflammatory factors in the model group,and The curative effect is better than that of adapalene gel in the positive control group,indicating that the short-term treatment of baicalin liposomes can reduce the level of inflammatory factors and can treat mild to moderate acne.ConclusionThis study clarified that baicalin is suitable for the development of liposome gels.The initially developed baicalin liposome gel has good pharmacological properties and has a certain slow-release effect.It is for the development of liposomes into liposome gel The experimental foundation is laid,and the pharmacodynamic test shows that it provides new pharmaceutical preparations for the clinical treatment of acne. |
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