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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。
Preparation of nimodipine / ligustrazine dual drug-loaded nanoparticles (NMD / TMP-NPs), investigate its pharmacokinetic behavior and brain tissue distribution, to explore the dual drug-loaded nanoparticles for improving the efficacy of the drug. In this study, NMD / TMP-NPs were prepared by double emulsion method. The entrapment efficiency and drug loading were measured by ultracentrifugation. The release of NMD / TMP-NPs was measured by dialysis. (NMD-NPs + TMP) suspension was used as the control group to study the in vivo pharmacokinetics and distribution of NMD in rats after intravenous injection of NMD / TMP-NPs suspension. The entrapment efficiency and drug loading of NMD in the prepared nanoparticles were (79.71 ± 0.73)% and (1.74 ± 0.02)%, respectively. The encapsulation efficiency and drug loading of TMP were (40.26 ± 1.51)% and (4.38 ± 0.16)%. After being made into nanoparticles, the in vitro release has the characteristics of sustained release. In vivo pharmacokinetics and tissue distribution of the main parameters: NMD suspension, NMD / TMP suspension, NMD-NPs suspension, (NMD-NPs + TMP) suspension, NMD / TMP-NPs suspension t1 / 2β were (1.097 ± 0.146), (1.055 ± 0.06), (1.950 ± 0.140), (1.860 ± 0.096) and (2.497 ± 0.475) h respectively, and the CL were 0.778 ± 0.098 and 1.133 ± 0.111 respectively 0.247 ± 0.023, 0.497 ± 0.040, 0.297 ± 0.024 h · L-1, respectively. The AUC0-∞ were (514.218 ± 60.383), (352.916 ± 33.691), (1818.429 ± 240.198), (804.110 ± 75.804 ), (1 349.058 ± 215.497) μg · h · L-1, respectively. The AUC0-t in each group was 0.301 9,0.624 8,1.068 6,1.313 0,1.046 5 mg · h · L -1, respectively. The results showed that NPs delayed the elimination of NMD in vivo. Adding TMP or preparing dual drug-loaded nanoparticles could significantly improve the in vivo pharmacokinetics of NMD and significantly increase the content of NMD in the brain.