神经毒素PLGA纳米粒的制备及鼻黏膜给药的药动学研究  

Studies on α-cobro-neurotoxin-loaded Poly(lactic-co-glycolic Acid) Nanoparticles: Preparation and Pharmacokinetics in vivo through Nasal Administration

作　　者：李范珠[1] 程巧鸳[1] 

机构地区：[1]浙江中医药大学药学系,杭州310053

出　　处：《浙江中医药大学学报》2006年第2期211-213,216,共4页Journal of Zhejiang Chinese Medical University

基　　金：国家自然科学基金资助计划项目(No:30371781)~~

摘　　要：[目的]探索可生物降解乳酸/羟基乙酸共聚物[poly(lactic-co-glycolic acid),PLGA]纳米粒(nanoparticle,NP)作为大分子蛋白质药物的载体经鼻黏膜给药的可能性。[方法]用复乳化-溶剂挥发法制备了神经毒素(α-cobro-neurotoxin,CNT)PLGA纳米粒(CNT-PLGA-NP);光子相关光谱法测定了Zeta电位和平均粒径;放射性计数法测定了CNT的包封率;考察了CNT-PL-GA-NP的体外释放特性;评价了CNT-PLGA-NP经鼻黏膜给药后的体内药动学过程。[结果]复乳化-溶剂挥发法制备的CNT-PLGA-NP大小均匀,表面光滑圆整,Zeta电位为-13.4mV,平均粒径为320.2nm,包封率为45%;CNT-PLGA-NP的体外释放分为两相,即突释释药相和缓释平台相;CNT、CNT-PLGA-NP和CNT-PLGA-NP-(B+T)的AUC及t1/2(β)分别为1.14、7.12、8.37μg·h/ml和20.06、44.14、34.82h,可见吐温-80和冰片有明显的促吸收作用。[结论]PLGA-NP可能成为神经毒素鼻黏膜给药的新型载体;吐温-80(T)和冰片(Borneol,B)可作为CNT-PLGA-NP鼻黏膜给药良好的吸收促进剂。[Objective] To investigate the possibility of [poly（lactic-co-glycolic acid） ,PLGA] nanoparticles （NP） as a new kind of protein drug carrier for nasal administration. [Method] CNT-PLGA-NP was prepared by double emulsification solvent evaporation. Its morphology was examined by transmission electronmicroscope （TEM）. In the use of photon correlation spectroscopy （PCS） and laser Doppler anemometry（LDA）,its Zeta potential and mean particle size were estimated. Also, the entrapment efficiency of CNT-PLGA-NP and its pharmacokinetics in rats through nasal administration were studied. [Result] The Zeta potential, mean particle size, entrapment efficiency of CNT-PLGA-NP were - 13. 4mV, 320. 20nm and 45% respectively . Its vitro CNT release from CNT-PLGA-NP appeared to consisting of two components with initial rapid release followed by a exponential stage. The AUC and t1/2 （β） of CNT, CNT-PLGA-Np and CNT-PLGA-NP（B＋ T） were 1.14, 8.37, 7.12μg·h/mL and 20.06, 44. 14, 34.82h respectively. [Conclusion]PLGA-NP might be a potential new drug carrier for CNT. Polysorbate 80 and borneol might be good absorption enhancers.

关 键 词：神经毒素 乳酸/羟基乙酸共聚物 纳米粒 鼻黏膜给药 药动学 吸收促进剂 

分 类 号：R962[医药卫生—药理学]