紫杉醇纳米脂质体在大鼠体内的药动学

目的对紫杉醇纳米脂质体在大鼠体内的药动学进行研究.方法大鼠尾静脉注射紫杉醇纳米脂质体及紫杉醇注射液,建立液相-质谱联用分析(LC-MS/MS)方法测定血浆中的紫杉醇药物浓度.结果血药浓度在0.2～1 000 μg·L-1范围内线性良好(r=0.999 6),方法回收率及提取回收率均大于90%,日内,日间精密度RSD＜15%.紫杉醇纳米脂质体及市售紫杉醇注射液血浓经时曲线均符合二室模型.t1/2α分别为(0.71±0.25)h和(0.438±0.023)h,t1/2β分别为(13.2±1.2)h和(7.8±1.4)h,AUC分别为(4 519.7±791.3)μg·L-1·h和(2 679.2±530.7 μg·L-1·h).结论本法灵敏度高,准确、可靠.与市售紫杉醇注射液相比,紫杉醇纳米脂质体有一定的长循环作用且可提高在大鼠体内的生物利用度.     

槲皮素长循环纳米脂质体的制备及大鼠体内药动学参数测定

目的 制备槲皮素长循环纳米脂质体(QUE-CNL),并测定其在大鼠体内的药动学参数.方法采用乳化蒸发 低温固化法制备QUE-CNL;高效液相色谱法测定槲皮素及QUE-CNL在大鼠体内不同时间点的血药浓度,用3p97药动学软件处理数据,计算药动学参数.结果QUE-CNL在大鼠体内血浆浓度显著高于槲皮素血浆浓度,QUE-CNL药 时曲线下面积较槲皮素大(P<0.01),表观分布容积较槲皮素低(P<0.01),血浆清除率较槲皮素慢(P<0.01).结论以乳化蒸发 低温固化法制备的QUE-CNL可延长槲皮素在血浆中循环时间.     

紫杉醇纳米脂质体的制备及其在小鼠体内组织分布

目的制备紫杉醇新型纳米脂质体并研究其在小鼠体内组织分布。方法采用薄膜分散超声结合冷冻干燥制备紫杉醇纳米脂质体。小鼠尾静脉注射紫杉醇脂质体及市售紫杉醇注射液Anzatax,RP-HPLC检测小鼠各组织中紫杉醇浓度。梯形法计算紫杉醇在小鼠各组织的蓄积情况。结果紫杉醇纳米脂质体粒径<100 nm,药物包封率>80%。小鼠经iv给予剂量为3 mg.kg-1的紫杉醇脂质体和普通紫杉醇注射液,紫杉醇纳米脂质体在肝脾系统轻微蓄积,肝脏AUC0→8h仅仅提高34%,脾脏AUC0→8h提高6%。结论紫杉醇纳米脂质体基本没有改变紫杉醇注射液的组织分布,有望为临床提供更安全有效的紫杉醇新制剂。     

阿苯达唑纳米脂质体冻干粉在大鼠体内药动学及肝靶向研究

目的：研究阿苯达唑纳米脂质体冻干粉在大鼠体内的药动学过程及肝脏靶向性。方法：大鼠以灌胃给予阿苯达唑片、阿苯达唑脂质体及阿苯达唑纳米脂质体冻干粉,分别于给药后不同时间点取血及肝脏,样品预处理后利用高效液相色谱（HPLC）法测定血浆及肝组织中药物浓度,考察3种制剂的药动学参数及肝靶向性差异。结果：阿苯达唑纳米脂质体冻干粉主要药动学参数如下：C_max为（7.05±0.70）μg·mL^-1,t_max为（6.15±0.66） h,AUC_0-∞为（150.9±12.1）μg·mL^-1·h,以阿苯达唑片、阿苯达唑脂质体为参比制剂,阿苯达唑纳米脂质体冻干粉相对生物利用度分别为236.04%和178.45%;肝靶向试验结果显示：阿苯达唑纳米脂质体冻干粉在肝组织中的分布显著高于阿苯达唑片和阿苯达唑脂质体。结论：将阿苯达唑脂质体制成纳米级脂质体冻干粉后,可显著提高药物的相对生物利用度和肝靶向性。     

辛伐他汀纳米脂质载体的制备及大鼠体内药动学

采用乳化溶剂蒸发法制备辛伐他汀(1)纳米脂质载体(1-NLC),考察了其理化特性、在体肠吸收特性和大鼠体内药动学.结果表明,1-NLC平均粒径为(72.1±47.2)nm,包封率为(94.6±2.5)％,载药量为(5.78±0.57)％.在体肠吸收研究表明,与原药相比,1-NLC在十二指肠、空肠和回肠的吸收速率常数分别提高了0.5、1.3和0.6倍.大鼠体内药动学研究表明,与1混悬液组相比,1-NLC组的1及其活性代谢物辛伐他汀酸的口服生物利用度分别为222％和269％.     

两性霉素B复合磷脂纳米脂质体Beagle犬体内药动学研究

目的 采用LC-MS/MS测定Beagle犬血浆中两性霉素B的含量,研究受试物两性霉素B复合磷脂纳米脂质体(liposomal amphotericin B,L-AmB)和参比药物AmBisome在Beagle犬体内的药动学行为。方法 选取成年健康Beagle犬12只,♀♂各半。采用双交叉试验设计,周期间洗脱期为2周。经前肢静脉注射给药(6 mg·kg^-1,1.0 mg·mL^-1),采集给药前以及给药后各时间点血浆样品,应用经验证的LC-MS/MS方法测定血浆中两性霉素B浓度,DAS 2.1.1中求算药动学参数。结果 Beagle犬静脉注射给予6 mg·kg^-1的受试物和参比药物后,动物体内两性霉素B的AUC_(0-t)分别为(705 520±178 252),(677 310±166 326)μg·h·L^-1;C_max分别为(142 683±29 823),(121 992±37 983)ng·mL^-1;t_1/2分别为(8.9±1.5),(9.7±0.6)h。结论 L-AmB及参比制剂AmBisome在Beagle犬体内的药动学参数差异无统计学意义。     

紫杉醇固体脂质纳米粒大鼠体内药动学

目的研究紫杉醇固体脂质纳米粒在大鼠体内的药动学。方法10只健康大鼠,雌雄各半,分为2组,分别口服给药紫杉醇固体脂质纳米粒和紫杉醇乳剂30 mg.kg-1,在设计的时间点从颈静脉取血,采用RP-HPLC测定紫杉醇在全血中的药物浓度,药动学参数用3P97软件进行处理。结果大鼠口服给药后,紫杉醇固体脂质纳米粒和乳剂的tm ax分别为3.133 h和1.627 h,MRT分别为10.362 h和3.297 h,mρax分别为1.512 2 mg.L-1和0.718 9 mg.L-1。结论固体脂质纳米粒能够显著改善大鼠体内紫杉醇的药动学行为,有利于其更好地发挥抗肿瘤作用。     

紫杉醇纳米脂质体凝胶剂的制备及体外透皮研究

目的制备紫杉醇纳米脂质体凝胶剂,考察其粒径、粒径分布、包封率、体外释放度及透皮特性。方法采用薄膜蒸发高压微射流法制备紫杉醇纳米脂质体,以卡波姆为凝胶基质,研制紫杉醇纳米脂质体凝胶剂,采用正交试验探索最佳工艺。用粒径测定仪测定脂质体的粒径及其粒径分布,低速-超速相结合法测定包封率,透析膜扩散法进行体外释放试验,以离体小鼠皮结合改良Franz扩散装置考察其体外透皮特性。结果紫杉醇纳米脂质体的最佳工艺:卵磷脂的含量为2%,药物与磷脂质量比为1∶30,磷脂与胆固醇的质量比为10∶1。测得的粒径为81.8 nm;粒径分布系数为0.180;平均包封率73.2%。纳米脂质体凝胶剂72 h累积释放百分率为79.04%;48 h的单位面积累积渗透量为429.68μg·cm?2。结论该制剂制备工艺简单,易于涂布,具有较高的包封率,粒径较小且分布均匀,体外释放缓慢。纳米脂质体能促进脂溶性药物紫杉醇透过皮肤。     

纳米脂质体研究进展

目的介绍纳米脂质体的最新研究进展。方法纳米脂质体由于在稳定性、吸收和体内分布等方面的特殊效应而受到药学工作者的青睐,相关人员对纳米脂质体做了大量的研究,并取得了较大的进展。参阅国内外代表性文献28篇,并对其进行分析、归纳和整理。结果对纳米脂质体的制备方法、靶向治疗以及给药途径等方面加以综述。结论随着科技的发展,纳米脂质体传递系统将会在临床治疗中发挥更大的作用。     

天麻素纳米脂质体的制备及其体外释药特性研究

目的:研制天麻素（GTD）纳米脂质体,提高GTD的脑靶向性。方法:用正交设计筛选GTD纳米脂质体的最优处方,对其质量进行评定,并考察其体外释药特性。结果:GTD最优处方组成为:药脂比为1:20,胆固醇:卵磷脂为3:3,药物浓度为60%（w/w）,水化介质为PBS,pH 6.5。由最优制得的GTD纳米脂质体外形圆整,平均粒径为（77.13±7.60）nm,Zeta电位为（-8.35±0.35）mV（n=3）,平均包封率为（65.22±1.63）%（n=9）。体外释药符合Higuchi方程:Q=-0.201 2+0.412 4t^1/2（r=0.980 0）,具有明显的缓释特性。结论:GTD处方组成简单,质量较好,具有缓释性,为进一步体内脑靶向性研究奠定了基础。     

紫杉醇自乳化微乳的制备及其在大鼠体内的药动学

目的:制备紫杉醇微乳,并对其急性过敏反应和大鼠体内的药动学进行考察。方法:三角相图法探讨了紫杉醇自乳化微乳(以下简称自微乳)的形成条件,采用均匀设计优化组成制备自微乳。以紫杉醇注射液对照,比较自微乳豚鼠的急性过敏反应和大鼠体内的药动学。结果: 以三辛酸甘油酯三丁酸甘油酯(1 ∶1)为油相,无水乙醇作助乳化剂制备的紫杉醇自微乳经生理盐水稀释后形成稳定的微乳,平均粒径为(16±s3)nm。以紫杉醇注射液作对照,自微乳豚鼠的急性过敏反应明显降低。统计矩分析,紫杉醇自微乳与紫杉醇注射液大鼠体内平均滞留时间分别为3. 89h和2. 52h,自微乳延长药物在大鼠体内的滞留时间。结论:通过优化处方制备的紫杉醇自微乳具有较好的稳定性,并可显著降低急性过敏反应。     

8-氯腺苷长循环脂质体的制备及其在大鼠体内的药代动力学

Aim To prepare 8-chloro-adenosine (8-Cl-A) long circulation liposomes with high entrapped efficiency and prolonged action-time of 8-Cl-A in vivo. Methods To prepare 8-Cl-A long circulation liposomes of Manometer size by improved multiple emulsion. The entrapped efficiency, size and size distribution of 8-Cl-A long circulation liposomes were determined, and its pharmacokinetics in rats was evaluated. Results The entrapped efficiency of 8-Cl-A long circulation liposomes was 62.70% and mean diameter of the liposomes was 79.9 rim. The pharmacokinetics studies indicated that 8-Cl-A long circulation liposomes showed higher drug concentration and larger AUC values than that of 8-Cl-A after iv to rats. Conclusion 8-Cl-A long circulation liposomes could prolong the action-time of 8-Cl-A in vivo.     

Preparation and ocular pharmacokinetics of ganciclovir liposomes

Ophthalmic liposomes of ganciclovir (GCV) were prepared by the reverse phase evaporation method, and their ocular pharmacokinetics in albino rabbits were compared with those obtained after dosing with GCV solution. The in vitro transcorneal permeability of GCV liposomes was found to be 3.9-fold higher than that of the solution. After in vivo instillation in albino rabbits, no difference was found in the precorneal elimination rate of GCV from liposome vs solution dosing. The aqueous humor concentration-time profiles of both liposomes and solution were well described by 2-compartmental pharmacokinetics with first-order absorption. The area under the curve of the aqueous humor concentration-time profiles of GCV liposomes was found to be 1.7-fold higher than that of GCV solution. Ocular tissue distribution of GCV from liposomes was 2 to 10 times higher in the sclera, cornea, iris, lens, and vitreous humor when compared with those observed after solution dosing. These results suggested that liposomes may hold some promise in ocular GCV delivery.     

紫杉醇超饱和自微乳化给药系统的制备及大鼠体内药动学研究

目的:制备紫杉醇超饱和自微乳化给药系统(supersaturatable self-microemulsifying drug delivery system,S-SMEDDS),并对其在大鼠体内的药动学进行研究。方法:采用伪三元相图的方法,优化紫杉醇自微乳化给药系统(SMEDDS)的处方。18只大鼠随机分为3组,分别灌胃给予10 mg/kg紫杉醇溶液、SMEDDS和S-SMEDDS,测定紫杉醇的血药浓度c、max、AUC和tmax,计算相对生物利用度。结果:确定紫杉醇SMEDDS最优处方为:油相∶表面活性剂∶助表面活性剂=50∶33∶17。油相为Lauroglycol FCC∶橄榄油(2∶1),表面活性剂为Cremophor EL∶吐温-80(1∶1),助表面活性剂为PEG-400。S-SMEDDS在此处方基础上添加5%羟丙基甲基纤维素。稀释对制剂的粒径无显著影响。SMEDDS和S-SMEDDS的粒径分别为(92.7±47.7)和(93.6±36.8)nm,粒径分布呈高斯分布。SMEDDS和S-SMEDDS的cmax和AUC显著高于溶液剂,tmax<溶液剂,生物利用度分别为333.9%和719.3%。结论:紫杉醇S-SMEDDS的口服吸收强于溶液剂和SMEDDS。     

Preparation and the in-vivo evaluation of paclitaxel liposomes for lung targeting delivery in dogs

Objectives The aim of this study was to develop paclitaxel liposomes for a lung targeting delivery system. Methods The liposomes composed of Tween‐80/HSPC/cholesterol (0.03 : 3.84 : 3.84, mol/mol), containing paclitaxel and lipids (1 : 40, mol/mol), were prepared by a combination of solid dispersion and effervescent techniques, and then subjected to ultrasonication. The pharmacokinetics and biodistribution of liposomal and injectable formulation of paclitaxel in dogs were studied after intravenous administration. Key findings The mean diameter, polydispersity index, zeta‐potential and entrapment efficiency of the liposomes were 501.60 ± 15.43 nm, 0.28 ± 0.02, ?20.93 ± 0.06 mV and 95.17 ± 0.32%, respectively. The liposomal formulation kept stable for at least 3 months at 6 ± 2°C and didn't cause haemolysis. The liposome carrier decreased the area under the curve and terminal half‐life of paclitaxel compared with paclitaxel injection ranging from 0.352 ± 0.031 mg/l*h and 0.0671 ± 0.144 h to 0.748 ± 0.062 mg/l*h and 1.978 ± 0.518 h, respectively. The paclitaxel liposomes produced a drug concentration in the lung that was markedly higher than that in other organs or tissues and was about 15‐fold of that of paclitaxel injection at 2 h. Conclusions To sum up, these results demonstrated that the paclitaxel liposomes are an effective lung targeted carrier in the treatment of lung cancer.     

Preparation of paraoxonase‐1 liposomes and studies on their in vivo pharmacokinetics in rats

A liposome formulation of the enzyme paraoxonase‐1 (PON1) was prepared for purposes of prolonging and maintaining its activity in vivo. Following purification of PON1 from rabbit serum, liposomes containing PON1 (L‐PON1) were prepared using a film‐dispersion method with a soybean phospholipid–cholesterol mixture (5 : 1, w/w). The pharmacokinetic behaviour of conventional injectable PON1 and L‐PON1 was compared following a single intravenous injection in rats. The enzyme activity of PON1 and its pharmacokinetic parameters were calculated based on a two‐compartment model following conventional injection. The level of PON1 encapsulation in L‐PON1 was 86.20 ± 3.12%. The particle size distribution of L‐PON1 was a narrow unimodal form, with an average diameter of 126 nm. The results suggest that compared with conventional injectable PON1, L‐PON1 has an improved half‐life and enhanced enzyme activity in rats. In conclusion, PON1 can be encapsulated into a lipid bilayer for enhanced stability.     

辣椒碱多囊脂质体的制备及在大鼠体内的药动学研究

目的 制备辣椒碱多囊脂质体,并考察其包封率和在大鼠体内的药动学.方法采用复乳法制备辣椒碱多囊脂质体、单因素筛选处方,并考察大鼠sc辣椒碱多囊脂质体后的体内药动学.结果制备的辣椒碱多囊脂质体的外观圆整,大小均匀,包封率为71.9%±3.8%,平均粒径为8.1 μm.大鼠sc辣椒碱多囊脂质体后,与辣椒碱溶液相比,Cmax分...     

Enhancement of radiotherapy efficacy by pleiotropic liposomes encapsulated paclitaxel and perfluorotributylamine

Paclitaxel (PTX) is widely used as a radiosensitizer in the clinical treatment of cancer. However, the efficacy of chemoradiotherapy is limited by the hostility of the tumor microenvironment such as hypoxia. To overcome this constraint, we designed pleiotropic radiotherapy sensitized liposomes containing perfluorotributylamine (PFTBA) and PTX. The results showed that liposomes significantly accumulated in the tumor site. PFTBA in liposomes dramatically reversed tumor hypoxia and improved the sensitivity of tumor radiotherapy. PTX in liposomes blocked the cell cycle of tumor cells in the radiation-sensitive G2/M phase, which was even greater when combined with PFTBA. In vitro and in vivo tumor treatment further demonstrated remarkably improved therapeutic outcomes in radiotherapy with such biocompatible liposomes. In conclusion, the pleiotropic liposomes encapsulated PFTBA and PTX provide significant radiotherapy sensitization and show promise for future application in clinical medicine.