【作者】 张奇志； 王美娜； 曹师磊； 高小玲； 蒋新国；

【Author】 ZHANG Qi-zhi WANG Mei-na CAO Shi-lei GAO Xiao-ling JIANG Xin-guo (Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai, 200032, China)

【机构】 复旦大学药学院药剂学教研室；

【摘要】 目的制备载有荧光标记物6-香豆素的壳聚糖修饰的聚乳酸纳米粒(chitosan-PLA-NP),并初步评价其鼻腔给药后的脑内递药特性。方法采用复乳-溶剂蒸发法制备chitosan-PLA-NP,测定其粒径分布、zeta电位、包封率、残余PVA、稳定性、鼻纤毛毒性及体外泄漏率。以聚乳酸纳米粒(PLA-NP)为对照,比较大鼠鼻腔给予两种纳米粒后各脑组织及血浆中6-香豆素的浓度。结果chitosan-PLA-NP形态圆整,粒径分布185.4±49.5nm,Zeta电位2.81mV,包封率71.2%,PVA残留量8.85%,在溶菌酶和鼻洗液中稳定,没有鼻纤毛毒性,在pH7.4和pH4条件下24h累积泄漏百分率<8%。大鼠鼻腔给予两种纳米粒后,chitosan-PLA-NP在各脑组织的AUC0→12h为PLA-NP的1.17~1.38倍,且各脑组织与血浆AUC的比值明显高于PLA-NP(p<0.01)。结论chitosan-PLA-NP能促进药物由鼻直接转运入脑,有望作为多肽蛋白药物鼻腔给药的载体。更多还原

【Abstract】 OBJECTIVE To develop a novel nasal protein carrier system, chitosan-coated polylactic acid nanoparticles (chitosan-PLA-NP). METHODS chitosan-PLA-NP was prepared by a double-emulsion/solvent evaporation technique and characterized in terms of size, zeta potential, drug entrapment efficiency, residual PVA, stability, in vitro leak and nasal ciliotoxicity. The nanoparticles encapsulated with 6-coumarin were administered intranasally to rats, and the concentrations of 6-coumarin in blood and brain tissues were monitored. RESULTS chitosan-PLA-NP containing 6-coumarin was generally spherical with a mean diameter of 185.4± 49.5 nm, a positive surface charge, 71.2% encapsulation efficiency, 8.85% residual PVA and no ciliotoxicity. It was stable in lysozyme and nasal washes after incubation 2 h at 37℃. In vitro leak was less than 8% within 24 h under two different pH conditions. The intranasal administration of chitosan-PLA-NP resulted in a 1.17~1.38-fold increase AUC0→12h in brain tissues, compared to PLA-NP. The ratios of AUC in brain tissues to that in plasma obtained after nasal application of chitosan-PLA-NP were significant higher than those of PLA-NP (p<0.01). CONCLUSION chitosan-PLA-NP demonstrated its potential on improving the efficacy of the direct nose-brain transport for drugs.更多还原