摘要
目的制备西罗莫司胶束,提高其溶解度,以适应其在眼部的应用。方法以聚山梨酯-80(Tween 80)和聚氧乙烯硬脂酸酯(P40S)为载体,采用薄膜分散法制备西罗莫司胶束。从粒径、PDI、X射线衍射图谱、红外光谱、包封率等方面对其进行表征。考察了其体外释放和离体兔巩膜渗透特性,并初步研究了兔眼前房药动学特征。结果测得胶束的平均粒径为(12. 36±0. 21) nm,平均电位为(-6. 08±0. 98) m V,包封率为(99. 6±0. 20)%,X射线衍射与红外光谱结果也表明几乎不存在游离药物。体外释药及兔巩膜渗透模型均符合Higuchi方程,房水药动学结果表明,西罗莫司胶束可在眼内达到并长时间维持治疗浓度。结论制备的西罗莫司眼用胶束适合眼部给药,有望成为角膜移植免疫排斥治疗的新剂型。
OBJECTIVE To prepare sirolimus micelles for the purpose of improving the solubility and applicability in the eye.METHODS Sirolimus micelles were prepared by thin-film dispersion with Tween-80 and polyoxyethylene stearate(P40 S)as carriers.Size distribution,X-ray diffraction spectra,IR spectra and encapsulation efficiency were used to evaluated the character of micelles.The in vitro release and scleral permeability were investigated,and the pharmacokinetics of micelles formulation in rabbit aqueous humor was preliminarily studied.RESULTS The average particle size was(12.36±0.21)nm,the mean potential was(-6.08±0.98)m V,and the entrapment efficiency was(99.6±0.20)%.Both X-ray diffraction and IR spectra showed that there was almost no free drug.The in vitro release and scleral permeation profiles were in accordance with Higuchi equation.The pharmacokinetic results of aqueous humor showed that sirolimus micelles could reach and maintain the therapeutic concentration in the eye for a long time.CONCLUSION The prepared sirolimus ophthalmic micelles is suitable for ocular administration and is expected to become a promising formulation in the treatment of immune rejection for corneal transplantation.
作者
王领
孙茹茹
汤湛
王俏
WANG Ling;SUN Ru-ru;TANG Zhan;WANG Qiao(Institute of Materia Medica,Zhejiang Academy of Medical Sciences,Hangzhou 310013,China;Zhejiang Jingxin Pharmaceutical Co.,Ltd.,Xinchang 312500,China)
出处
《中国药学杂志》
CAS
CSCD
北大核心
2019年第8期638-645,共8页
Chinese Pharmaceutical Journal
基金
浙江省科技计划项目资助(2017F30005)
浙江省药学会项目资助(2018ZYY16)
关键词
西罗莫司
眼用制剂
抗免疫排斥
胶束
增溶缓释
sirolimus
ophthalmic preparation
anti-immune rejection
micelles
solubilization and sustained release
