中国中药杂志

2016, v.41(22) 4254-4258

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尼莫地平/川芎嗪双载药纳米粒的体内药动学和脑组织分布研究
Pharmacokinetics and brain distribution of NMD/TMP-nanoparticles

何雯洁;洪倩;梁静;何晓玮;朱逢佳;
HE Wen-jie;HONG Qian;LIANG Jing;HE Xiao-wei;ZHU Feng-jia;Zhejiang Hospital;The First Hospital Affiliated to Huzhou Teachers' University;

摘要(Abstract):

制备尼莫地平/川芎嗪双载药纳米粒(NMD/TMP-NPs),考察其体内药动学行为和脑组织分布情况,探讨双载药纳米粒用于提高药物疗效的可能性。该试验采用复乳法制备NMD/TMP-NPs,超速离心法测其包封率和载药量,透析法测其体外释放,并以NMD混悬液、NMD/TMP混悬液、NMD-NPs混悬液、(NMD-NPs+TMP)混悬液为对照组,考察大鼠尾静脉注射NMD/TMP-NPs混悬液后NMD的体内药动学行为和脑内分布情况。所制备纳米粒中NMD的包封率和载药量分别为(79.71±0.73)%,(1.74±0.02)%,TMP的包封率和载药量为(40.26±1.51)%,(4.38±0.16)%;制成纳米粒后,其体外释放具有缓释特点。体内药动学和组织分布主要参数:NMD混悬液、NMD/TMP混悬液、NMD-NPs混悬液、(NMD-NPs+TMP)混悬液、NMD/TMP-NPs混悬液t1/2β分别为(1.097±0.146),(1.055±0.06),(1.950±0.140),(1.860±0.096),(2.497±0.475)h,CL分别为(0.778±0.098),(1.133±0.111),(0.247±0.023),(0.497±0.040),(0.297±0.024)h·L-1,AUC0-∞分别为(514.218±60.383),(352.916±33.691),(1 618.429±240.198),(804.110±75.804),(1 349.058±215.497)μg·h·L-1;各组脑内AUC0-t分别为0.301 9,0.624 8,1.068 6,1.313 0,1.046 5 mg·h·L-1。结果表明NPs延缓了NMD在体内的消除,加入TMP或制备为双载药纳米粒均可明显改善NMD体内药动学行为,并显著提高NMD脑内含量。
This study aims to prepare nimodipine/tetramethylpyrazine-loaded poly( D,L-lactide-co-glycolide) dual-drug nanoparticles( NMD / TMP-NPs) and investigate pharmacokinetics and brain distribution to evaluate the possibility of enhancing the drug effect of dual-drug nanoparticles. NMD / TMP-NPs were prepared via W / O / W emulsion solvent evaporation. Entrapment efficiency and drug loading of NMD / TMP-NPs were investigated by ultracentrifugation,and drug release behavior in vitro was studied by dialysis method.The pharmacokinetic and brain distribution were studied in SD mice administered intravenously with NMD / TMP-NPs in comparison with NMD-suspension,NMD / TMP-suspension and NMD-NPs,( NMD-NPs + TMP)-suspension. According to the results,the entrapment efficiency and drug loading of NMD were( 79. 71 ± 0. 73) %,( 1. 74 ± 0. 02) %,those of TMP were( 40. 26 ± 1. 51) % and( 4. 38 ±0. 16) %. The nanoparticles showed the property of sustained release. On the basis of the major parameters for in vivo pharmacokinetic and brain distribution,t1 /2βof NMD-suspension,NMD / TMP-suspension and NMD-NPs,( NMD-NPs + TMP)-suspension,NMD / TMPNPs were( 1. 097 ± 0. 146),( 1. 055 ± 0. 06),( 1. 950 ± 0. 140),( 1. 860 ± 0. 096),( 2. 497 ± 0. 475) h,CL were( 0. 778 ±0. 098),( 1. 133 ± 0. 111),( 0. 247 ± 0. 023),( 0. 497 ± 0. 040),( 0. 297 ± 0. 024) h·L- 1,AUC0-tin rat plasma were( 514. 218 ±60. 383),( 352. 916 ± 33. 691),( 1 618. 429 ± 240. 198),( 804. 110 ± 75. 804),( 1 349. 058 ± 215. 497) μg·h·L- 1,respectively,and AUC0-tin brain were 0. 301 9,0. 624 8,1. 068 6,1. 313 0,1. 046 5 mg·h·L- 1,respectively. According to the in vivo study,the pharmacokinetic behavior of NMD were markedly prolonged by adding TMP or prepared dual-drug nanoparticles.

关键词(KeyWords): 川芎嗪;尼莫地平;双载药纳米粒;药动学;脑内分布
nimodipine;tetramethylpyrazine;dual-drug nanoparticle;pharmacokinetics;brain distribution

Abstract:

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基金项目(Foundation): 浙江省自然科学基金项目(LQ12H25001)

作者(Author): 何雯洁;洪倩;梁静;何晓玮;朱逢佳;
HE Wen-jie;HONG Qian;LIANG Jing;HE Xiao-wei;ZHU Feng-jia;Zhejiang Hospital;The First Hospital Affiliated to Huzhou Teachers' University;

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