荷叶碱脂质体的制备及体外释放性能研究

Preparation of Nuciferine Liposomes and Optimization of Formulation and Technology

目的为了降低荷叶碱的消除速度,提高其生物利用度,制备荷叶碱脂质体(Nuc-Lip)并研究其体外释放性能。方法以薄膜分散法制备Nuc-Lip,通过单因素考察药脂比、胆固醇用量、孵育时间、超声条件、胆酸钠用量和肉豆蔻酸异丙酯用量对荷叶碱包封率和载药量的影响。以包封率和粒径为评价指标,采用正交试验对Nuc-Lip进行处方工艺优化,并评价其体外释放性能。结果经最优处方工艺制备的Nuc-Lip呈球形,分布均匀,粒径为(37.08±1.36)nm,PDI为(0.094±0.007),Zeta电位为(-20.1±0.3)mV,包封率为(80.25±3.0)%、载药量为(2.33±0.09)%;Nuc-Lip体外释药缓慢,在24 h时累积释放达75.58%,符合一级释药模型。结论采用最优处方工艺制备的Nuc-Lip稳定可行,具有明显的缓释特征,为荷叶碱进一步开发提供了实验基础和理论依据。

OBJECTIVE In this study,nuciferine liposomes(Nuc-Lip)were prepared to reduce the elimination speed of nuciferine and improve its bioavailability.And its in vitro release properties were investigated.METHODS Nuc-Lip were prepared by the thin-film dispersion method.The encapsulation efficiency and drug loading of nuciferine were investigated by a single factor of drug-to-lipid ratio,cholesterol dosage,incubation time,ultrasonic conditions,sodium cholate dosage and isopropyl myristate dosage.Taking encapsulation efficiency and particle size as evaluation indicators,the orthogonal test was used to optimize the formulation process of Nuc-Lip,and to evaluate its in vitro release performance.RESULTS Nuc-Lip were prepared by the optimal formulation process was spherical and uniformly distributed.The particle size was(37.08±1.36)nm,the PDI was(0.094±0.007),the Zeta potential was(-20.1±0.3)mV,the encapsulation efficiency was(80.25±3.0)%,drug loading was(2.33±0.09)%.Nuc-Lip released slowly in vitro,with a cumulative release of 75.58%at 24 h,which is in line with the first-level drug release model.CONCLUSION Nuc-Lip prepared by the optimal formulation process is stable and feasible,has obvious sustained-release characteristics,and provides an experimental and theoretical basis for the further development of nuciferine.