盐酸西替利嗪脂质体凝胶的制备及初步药理学研究

Preparation and Pharmacological Research of Cetirizine Hydrochloride Liposome Gel

目的探讨盐酸西替利嗪脂质体凝胶的制备方法,并进行质量评价和初步药效考察。方法采用薄膜分散法制备盐酸西替利嗪脂质体溶液,在单因素试验基础上以大豆卵磷脂与胆固醇质量比、盐酸西替利嗪用量、水化时间、磷酸盐缓冲液(PBS)用量为考察因素,包封率为考察指标,采用正交试验优化脂质体制备处方;以卡波姆-940为凝胶基质制备盐酸西替利嗪脂质体凝胶,观察其外观性状,测定pH,并通过离心试验及温度试验观察凝胶的稳定性。取24只C57BL/6小鼠,分为空白对照组(等体积生理盐水)、阳性对照组(5%米诺地尔酊,1 mL/次)、实验组(盐酸西替利嗪脂质体凝胶,1 g/次),脱毛24 h后各组涂相应药物或生理盐水,每日1次,连续18 d。实验过程中,观察小鼠背部脱毛部位皮肤颜色变化及毛发生长情况,并于第4,6,10,13 d拍照;给药过程中,密切观察小鼠给药部位皮肤是否出现红肿、水疱或溃烂等接触性皮炎症状,以及小鼠生活习性等方面的改变。结果盐酸西替利嗪脂质体最佳制备工艺为,大豆卵磷脂250 mg,胆固醇50 mg,盐酸西替利嗪25 mg,PBS 5 mL,水化温度50℃,水化0.5 h;在该条件下制备的脂质体平均包封率为74.11%,平均载药量为5.12%,粒径为(174.6±1.2)nm,Zeta电位为(-43.2±1.6)mV,多分散系数为0.263±0.013。脂质体凝胶处方为,卡波姆-9400.2 g,盐酸西替利嗪脂质体溶液10 mL,甘油2 g,尼泊金乙酯16 mg,加蒸馏水至20 g,加三乙醇胺0.35 g调pH和稠度。制得的脂质体凝胶稳定性良好。初步药效实验结果表明,该脂质体凝胶可缩短模型小鼠皮肤变灰及毛发初长时间,且小鼠无接触性皮炎症状及生活习性改变。结论该盐酸西替利嗪脂质体凝胶制备工艺简单,质量稳定,改善模型小鼠的脱发效果较好。该结果可为雄激素性脱发经皮制剂的开发提供依据。

Objective To investigate the preparation method of the cetirizine hydrochloride liposome gel,and to evaluate its quality and efficacy.Methods The cetirizine hydrochloride liposome solution was prepared by the thin-film dispersion method.Based on the single factor test,the formulation of the liposome was optimized by the orthogonal test with the mass ratio of soybean lecithin to cholesterol,the dosage of cetirizine hydrochloride,hydration time,the dosage of phosphate buffer solution(PBS)as the factors and with the entrapment rate as the index.Cetirizine hydrochloride liposome gel was prepared with carbomer-940 as gel matrix.The stability of cetirizine hydrochloride liposome gel was evaluated by observing appearance properties,determining pH value,centrifugal test and temperature test.Twenty-four C57BL/6 mice were divided into the blank control group(equal volume of normal saline),the positive control group(5%minoxidil tincture,1 mL each time)and the experimental group(cetirizine hydrochloride liposome gel,1 g each time).24 h after depilation,the mice in each group were coated with corresponding drugs or normal saline once a day for 18 d.During the experiment,the changes in skin color and hair growth at the back depilation site of mice were observed,and photos were taken on the fourth,sixth,tenth and thirteenth days.During the administration,the skin of mice at the administration site was closely observed to judge whether there were contact dermatitis symptoms such as swelling,blisters or ulcers,and the changes in living habits of mice were observed.Results The optimal preparation process of cetirizine hydrochloride liposomes was as follows:250 mg of soybean lecithin,50 mg of cholesterol,25 mg of cetirizine hydrochloride,5 mL of PBS hydrated at 50℃for 0.5 h.The average entrapment rate of the liposome solution prepared under this condition was 74.11%,the average drug loading was 5.12%,the particle size was(174.6±1.2)nm,the Zeta potential was(-43.2±1.6)mV,and the polydispersity index(PDI)was 0.263±0.013.The formulation of liposome gel was as follows:0.2 g of carbomer-940,10 mL of cetirizine hydrochloride liposome solution,2 g of glycerol,16 mg of ethyl paraben,adding distilled water to 20 g,and finally adding 0.35 g of triethanolamine to adjust pH and consistency.The prepared liposome gel had good stability.The results of the preliminary pharmacodynamic test showed that the liposome gel could shorten the time of skin graying and hair growth of model mice,and the mice had no contact dermatitis symptoms and life habits changes.Conclusion The cetirizine hydrochloride liposome gel prepared in this study has the advantages of simple process,stable quality,which can significantly improve the alopecia in model mice.The results of the study can provide a basis for the development of transdermal preparations for androgenic alopecia.