盐酸普萘洛尔脂质体凝胶的制备及评价

Preparation and Evaluation of Propranolol Hydrochloride Liposomal Gel

制备用于治疗婴幼儿血管瘤的盐酸普萘洛尔脂质体凝胶并对其质量进行评价。采用薄膜分散法制备盐酸普萘洛尔脂质体,考察透射电镜下的形态,动态光散射仪测定粒径、Zeta电势,高效液相测定包封率、载药量。将制备的脂质体与2%卡波姆934凝胶混匀,用三乙醇胺调节pH 7.0~8.0,制备盐酸普萘洛尔脂质体凝胶。通过对脂质体凝胶进行离心实验、光照及温度实验确定影响其稳定性的因素。通过离体透皮实验,研究脂质体凝胶与普通凝胶的体外渗透速率与皮肤滞留量。结果:制备的脂质体透射电镜下成圆整的球状,脂质体粒径在(237.6±0.3)nm,多分散系数为(0.234±0.014),Zeta电势为(-26.82±0.38)mv。包封率为(48.40±0.12)%,载药量为(14.47±0.03)%。脂质体凝胶在离心、光照及温度实验中外观与药物含量无显著性差异。离体透皮实验中,脂质体凝胶与药物凝胶的稳态渗透速率分别为(7.43±0.12)μg/(cm^2·h)、(5.62±0.15)μg/(cm^2·h),在12 h,皮肤的滞留量分别为(22.56±0.23)μg/cm^2、(11.26±0.17)μg/cm^2。盐酸普萘洛尔脂质体凝胶能显著增加药物的渗透速率与皮肤滞留量,是一种有很大发展前景的经皮给药的系统。

To develop propranolol hydrochloride(PRO) liposomal gel for the treatment of infantile hemangioma(IH) and to evaluate its permeation on transdermal delivery in vitro PRO liposomal gel was prepared with the traditional film dispersion method using cholesterol,phosphatidyl ethanolamine and the drug.Its morphology was investigated with transmission electron microscope(TEM).The partical size and Zeta potential were conducted by means of dynamic light scattering.Entrapment efficiency and drag loading were measured by high performance liquid chromatography(HPLC).The 2%Carbopor 934 was added as a supportive base with the liposomes to prepare liposomal gel.The PRO liposomal gel was immediately neutralized with triethanolamine until pH value 7.0 ~8.0 after the liposomes and Carbopor were mixed well.The sample impress factor testings were performed under experiments of centrifugation,light and heat to find the main factors.The permeation of excised skin was conducted to compare skin permeation behavior and concentration in the skin of PRO liposomal gel with that of common gel.The liposomes were spherical and there were no adherences with others.The lipid bilayer can be clearly observed using TEM.The mean partical size,polydispersity index and Zeta potential were(237.6±0.3) nm,(0.234 ±0.014) and(-26.82 ± 0.38) mv respectively.The mean entrapment efficiency and drug loading were(48.40 ±0.12%) and(14.47 ±0.03%).The PRO liposomal gel was uniform and the content had no significant change when tested in experiments of centrifugation,light and heat.The steady penetration rate of the PRO liposomal gel and the PRO gel were(7.43 ±0.12) μg/(cm^2·h) and(5.62 ±0.15) μg/(cm^2·h),while the concentration in the skin were(22.56 ±0.23) μg/cm^2· and(11.26 ±0.17) μg/cm^2.PRO liposomal gel had a good skin permeation rate and concentration in the skin which can prolong the time taking drug and improve patient compliance.It will be a promising carrier of transdermal delivery for PRO in the future.