三磷酸腺苷脂质体鼻用凝胶制备及其抗缺氧作用  

Preparation of adenosine triphosphate liposome hydrogel and research of its anti-hypoxia effect

作　　者：欧歌 马金秋 朱林 李瑞滕 李欣[1] 杜丽娜 OU Ge;MA Jin-qiu;ZHU Lin;LI Rui-teng;LI Xin;DU Li-na(Department of Pharmacy,General Hospital of the Chinese People’s Liberation Army,Beijing 100853,China;Academy of Military Medical Sciences,Academy of Military Sciences,Beijing 100850,China;College of Pharmacy,Shandong University of Traditional Chinese Medicine,Jinan 250355,China)

机构地区：[1]解放军总医院药学部,北京100853 [2]军事科学院军事医学研究院,北京100850 [3]山东中医药大学药学院,山东济南250355

出　　处：《药学学报》2020年第6期1288-1295,共8页Acta Pharmaceutica Sinica

基　　金：全军医药卫生“十二五”面上项目(CWS11J303)。

摘　　要：制备三磷酸腺苷(adenosine triphosphate,ATP)脂质体,评价其对缺氧性脑损伤的治疗作用。采用离子对薄膜分散法制备ATP脂质体,其最优处方:三磷酸腺苷二钠、十六烷基三甲基溴化铵、大豆磷脂、胆固醇的质量比为1∶1.98∶8∶3,此时ATP脂质体包封率为(81.50±0.82)%,载药量为(6.79±0.07)%。通过体外释放实验与流变学测定分别考察ATP脂质体与空白凝胶的理化性质;将ATP脂质体、ATP水溶液分别加入甲基纤维素凝胶中,以甲基纤维素凝胶为阴性对照,进行小鼠鼻腔给药。动物实验获得军事医学研究院伦理委员会批准。连续给药9天后,与空白凝胶或ATP水凝胶相比,ATP脂质体水凝胶显著提高了血中红细胞与血红蛋白数值(P<0.01);连续给药13天后,在常压密闭缺氧实验中,与ATP水凝胶或空白凝胶相比,ATP脂质体鼻用凝胶能显著提高小鼠标准缺氧耐受时间(P<0.05)。小鼠海马促凋亡基因p53免疫组化染色显示,ATP脂质体对脑组织有明显保护作用。结果表明,ATP脂质体鼻用凝胶预防给药能明显提高小鼠耐缺氧能力,是一种前景广阔的抗缺氧制剂。The adenosine triphosphate(ATP)liposome,prepared with the methods of film dispersion and ionpairing was evaluated for its therapeutic effect on hypoxic brain damage.The appropriate formulation is adenosine disodium triphosphate,hexadecyl trimethyl ammonium bromide,soybean phospholipid,cholesterol with mass ratio of 1∶1.98∶8∶3.The encapsulation efficiency of ATP liposome was(81.50±0.82)%and the loading efficiency was(6.79±0.07)%.In vitro release test and rheology test were conducted to investigate the physicochemical properties of ATP liposomes and empty gels respectively.The blank methylcellulose gel,followed with ATP liposome and ATP aqueous solution added to the methycellulose gel,were used for nasal administration in mice respectively.All experiments were approved by the Ethics Committee for Experimental Research in Academy of Military Medical Sciences.After 9 days of continuous administration,ATP liposome hydrogel increased the values of red blood cells and hemoglobin(P<0.01)compared to ATP hydrogel and blank gel.And the ATP liposome hydrogel significantly increased the standard hypoxia tolerance time in mice compared to ATP hydrogel and blank gel after 13 days of nasal administration(P<0.05).The immunohistochemical staining of mice hippocampus for the proapoptotic gene p53 showed that ATP liposome hydrogel was capable of protecting brain tissue in hypoxia.It is indicated that the prophylactic administration of ATP liposome nasal gel can significantly improve the hypoxia tolerance of mice,and the ATP liposome nasal gel was proved to be a promising anti-hypoxia preparation.

关 键 词：三磷酸腺苷 脂质体 鼻内给药 水凝胶 缺氧 

分 类 号：R943[医药卫生—药剂学]