GnRH受体拮抗剂LXT-101缓释多囊脂质体的制备及体外评价

Multivesicular liposome sustained delivery of a novel synthetic electropositive GnRH antagonist LXT-101: preparation and in vitro evaluation

采用物理测定方法探讨正电性合成多肽LXT-101与磷脂膜的相互作用并进行LXT-101多囊脂质体(DepoLXT-101)的处方工艺筛选,同时进行体外评价。采用zeta电位法和荧光光谱法测定LXT-101分子与磷脂双分子膜的相互作用,复乳法制备DepoLXT-101,HPLC法测定DepoLXT-101的包封率并对DepoLXT-101进行形态和粒径分布测定;以生理盐水为介质测定LXT-101多囊脂质体体外释放行为。LXT-101分子与磷脂双分子膜的相互作用主要为静电吸附作用,通过在第二水相加入少量阴离子表面活性剂可以提高复乳稳定性,改善药物对多囊脂质体形成的不良影响;制备的DepoLXT-101呈球形多囊室结构,粒径分布较窄,大多数粒子(95%)的粒径分布在5～20μm,包封率较高。DepoLXT-101在37℃生理盐水介质中缓慢释药11d以上,累积释放率达到70%～90%。本实验所设计的方法可以用于制备合成正电性多肽多囊脂质体。

Using a simple method to determine the interaction between peptide and lipid bilayer and then deciding how to modify formulation from classic DepoFoam technology, multivesicular liposome of LXT-101 （DepoLXT-101） was prepared and characterized by in vitro evaluation. The electrostatic adsorption between peptide and lipid bilayer was observed by zeta potential and fluorescence spectrum. Anionic surfactants were added to stable the multiple emulsion and minimize the opposite effects resulted from drug. Encapsulation efficiency was determined by RP-HPLC. Morphology, particle size of DepoLXT-101 particles were characterized and their in vitro release was studied in sodium chloride solution. The DepoLXT-101 particles were prepared with good encapsulation efficiency, narrow size distribution and multivesicular construction. Over 95% of the DepoLXT-101 particles were in a size range of 5？20 μm. The in vitro assay in sodium chloride solution at 37 ℃ showed that 70%？90% of the peptide was released from particles slowly over 11 days. Multivesicular liposome sustained delivery of synthetic cationic peptides could be successfully prepared by the method.