PLA-α-细辛脑纳米粒的制备、表征及其对鼻黏膜的毒性  

Preparation,Characterization of PLA-α-asarone Nanoparticles and Its Toxicity to Nasal Mucosa

作　　者：陆瑾[1,2] 展冠军[2] 郭立玮[3] 付廷明[3] 朱国龙[2] LU Jan ZHAN Guan-jun GUO Li-wei FU Ting-ming ZHU Guo-long(Nanjing Dachang Hospital, Nanjing 210048, China Zhongda Hospital, Southeast University, Nanjing 210009, China Nanjing University of Chinese Medicine, Nanjing 210023, China)

机构地区：[1]南京市大厂医院,南京210048 [2]东南大学附属中大医院,南京210009 [3]南京中医药大学,南京210023

出　　处：《中国实验方剂学杂志》2017年第10期22-28,共7页Chinese Journal of Experimental Traditional Medical Formulae

基　　金：南京市药学会项目(2016YX009)

摘　　要：目的:表征聚乳酸-α-细辛脑(PLA-α-细辛脑)纳米粒,评价其鼻腔给药后鼻黏膜毒性,为其通过鼻腔给药方式用于体内的研究提供基础。方法:采用有机溶剂挥发法将α-细辛脑制备成PLA-α-细辛脑纳米粒,通过粒径分布、载药量和包封率评价纳米粒的工艺条件;红外光谱,差示扫描量热分析,X射线衍射分析及体外溶出试验分析药物在纳米粒中的分布状态;鼻纤毛毒性及鼻黏膜病理切片研究PLA-α-细辛脑纳米粒混悬液鼻腔给药后的鼻黏膜毒性。结果:α-细辛脑纳米粒平均粒径265.4 nm,多分散系数(PDI)0.038,载药量12.40%,包封率55.86%,α-细辛脑以分子状态分散或非晶型状态存在于PLA载体中,体外释放包括速释和缓释,呈双相动态,PLA-α-细辛脑纳米粒混悬液鼻腔给药后对鼻黏膜组织无明显的毒性作用。结论:有机溶剂挥发法制备的PLA-α-细辛脑纳米粒表征与鼻黏膜毒性试验结果表明该制剂适合于鼻腔给药。Objective： To prepare and characterize polylactic acid（PLA）-α-asarone nanoparticles,then to evaluate the its toxicity to nasal mucosa after intranasal administration. Method： α-Asarone was prepared to PLA-α-asarone nanoparticles by organic solvent evaporation method. The average particle size,drug loading and encapsulation efficiency of α-asarone nanoparticles were used to evaluate process conditions of the nanoparticles. Infrared spectroscopy, differential scanning calorimetry analysis, X-ray diffraction and in vitro dissolution test were researched to analyze the state of α-asarone in the nanoparticles. Nasal mucosa and mucosa cilia pathological were used to evaluate the nasal mucosal toxicity after nasal administration of PLA-α-asarone nanoparticles suspension. Result： The average particle size of PLA-α-asarone nanoparticles was 265. 4 nm,polydispersity index（PDI） was 0. 038,drug loading and encapsulation efficiency were 12. 40% and 55. 86%,respectively. α-Asarone existed in the nanoparticles in the form of molecular or amorphous state. In vitro release of PLA-α-asarone nanoparticles was biphasic dynamics,which included the immediate-release and sustained-release.PLA-α-asarone nanoparticles had no significant toxicity on nasal mucosa. Conclusion： The results of characterization and nasal mucosal toxicity on PLA-α-asarone nanoparticles prepared by organic solvent evaporation method indicate that the preparation is suitable for intranasal administration.

关 键 词：Α-细辛脑 纳米粒 鼻腔给药 鼻黏膜毒性 溶剂挥发法 包封率 聚乳酸 

分 类 号：R283.6[医药卫生—中药学] R284.1[医药卫生—中医学]