摘要
目的制备羟基积雪草酸固体脂质纳米粒(madecassic acid solid lipid nanoparticles,MA-SLN)并对其体外释药行为进行研究。方法(1)采用溶剂乳化挥发-高压均质法制备羟基积雪草酸固体脂质纳米粒,以包封率、载药量为指标,通过Box-Behnken响应面法筛选制备羟基积雪草酸固体脂质纳米粒的最优工艺及处方,并通过包封率、微观形态、粒径分布和Zeta电位对其质量进行评价。(2)配制羟基积雪草酸溶液为对照考察两种剂型中羟基积雪草酸的体外释放及透皮行为。结果(1)优化处方为羟基积雪草酸230.87 mg,山嵛酸甘油酯300 mg,P 188与T-80用量比为1∶1。羟基积雪草酸固体脂质纳米粒透射电镜下呈球状或类球状,平均粒径为(226.8±11.2)nm,PDI为(0.19±0.08),Zeta电位为(-25.11±3.24)mV。呈淡蓝色乳光,包封率84.1%,载药量21.5%。(2)两种剂型中羟基积雪草酸的体外累积释放24 h是75.63%,而溶液剂在4 h时已达97.36%;经皮稳态渗透速率分别为0.9754和0.6185μg·cm^(-2)·h^(-1),皮内滞留量分别为(5.73±0.32)和(2.73±0.56)μg/cm 2。结论羟基积雪草酸固体脂质纳米粒使难溶性的羟基积雪草酸体外释药显缓释特征,且皮肤渗透及皮内滞留量较溶液剂有显著提高,为下一步研制纳米凝胶剂打下了良好基础,有望成为治疗增生性瘢痕的一种新方法。
Objective To optimize the preparation process of madecassic acid-loaded solid lipid nanoparticles(MA-SLN)by response surface method and investigate the transdermal absorption behavior.Methods 1)The solid lip‐id nanoparticles of madecassic acid was prepared by solvent emulsification volatilization-high pressure homogeniza‐tion method,the formulation was optimized by Box-Behnken response surface method with encapsulation efficiency and drug loading as indicator.The particle size distribution,zeta potential,morphology were examined.2)Madecassic acid solution was prepared as control to investigate the in vitro release and transdermal behavior of madecassic acid through the excised pig ear skin.Results 1)The optimized prescription madecassic acid was 230.87 mg,and 300 mg of glyceryl behenate,the dosage ratio of P 188 to T-80 was 1:1.MA-SLN was spherical or spheroidal under transmission electron microscope.The average particle size was(226.8±11.2)nm,PDI was(0.19±0.08),Zeta potential was(-25.11±3.24)mV,2)The results showed that the MA release curves from the MA-SLN exhibited an obvious sustained release of MA in physiological media with no evidence of burst effect,and only 75.63%of MA was released from the MA-SLN at 24 h in pH 7.4 PBS,while 97.36%of MA at 4 h was released from the common solution.The average steady-state fluxes of madecassic acid from the liposomal gel and common solution were 0.9754 and 0.6185μg·cm^(-2)·h^(-1),respec‐tively.The skin retention of above preparations were(5.73±0.32)and(2.73±0.56)μg/cm^(2),respectively.Conclusions Madecassi c acid solid lipid nanoparticles could realize the sustained release and transdermal absorption of the insoluble drug madecassic acid,and lay the foundation for further development of nanogel,which suggested a promising poten‐tial of this drug delivery system to treat hypertrophic scar.
作者
彭祎婧
罗怀青
丁劲松
黎绫
赵雅芝
胡明华
马宁
PENG Yijing;LUO Hu aiqing;DING Jinsong;LI Ling;ZHAO Yazhi;HU Minghua;MA Ning(Hunan key laboratory of the research and development of novel pharmaceutical preparations,Changsha Hunan 410219,China;Changsha Jingyi Pharmaceutical Technology Co.,Ltd,Changsha Hunan 410000,China)
出处
《转化医学杂志》
2021年第5期318-323,共6页
Translational Medicine Journal
基金
湖南省教育厅重点项目(18A495)
长沙市科技局项目(kq1901111)
湖南省普通高等学校“十三五”专业综合改革试点项目(湘教通(2018)255号)
2020年湖南省学位与研究生教育改革研究项目(湘教通〔2020〕216号)。
