We previously reported the synthesis of three DOX conjugates that represented different targeting vehicles and showed them to have antitumor activity both in vitro and in vivo. However, the relationships between the pharmacokinetics of these DOX conjugates and their chemical structures were not characterized. In the current study, free DOX derived from each of the conjugates was found at low levels in the rat circulatory system, with conjugated DOX being the major form. The two polyethylene glycol (PEG) conjugates slowly released DOX, and t1/2β for total DOX from DOX-LNA, PEG-ami-DOX, and PEG-hyd-DOX was 5.79, 10.22, and 15.18 h, respectively. All three conjugates also deposited less DOX into normal organs than did an equivalent dose of free DOX, and the Cmax value of free DOX released by DOX- LNA, PEG-ami-DOX, and PEG-hyd-DOX was 32.5, 9.5, and 4.7 μg/g, respectively. Among the conjugates, the compound with an acid-labile bond between PEG and DOX exhibited the lowest free DOX deposition in healthy tissues, which should decrease the systemic toxicity of free DOX while allowing for tumor targeting by PEG.

BACKGROUND:The clinic therapeutic effect of resveratrol is limited due to its low oral bioavailability. Piceid, a precursor of resveratrol, is the most abundant form of resveratrol in nature. A number of studies have hypothesized that piceid may have the same bioactivities like those of resveratrol. The aim of this work is to compare piceid with resveratrol in antioxidation and antiproliferation activities in vitro.METHODS:The antioxidative effects of resveratrol and piceid were evaluated by phenanthroline-Fe²⁺ method and H₂O₂-induced oxidative injury cell model. The antiproliferation effects were determined by MTT method in human liver tumor HepG2 cells, human breast cancer MDA-MB-231 cells and MCF-7 cells. The effects of resveratrol and piceid on the cell cycle and the apoptosis were evaluated by flow cytometry. Additionally, the uptake profiles of resveratrol and piceid in cancer cells were observed using fluorescence microscopy and clarified by LC-MS/MS.CONCLUSION:Piceid exhibited higher scavenging activity against hydroxyl radicals than resveratrol in vitro. Resveratrol showed a significant protective effect against H₂O₂-induced cell damage. What is more, resveratrol had biphasic effects on tumor cells. Resveratrol and piceid only showed significant cytotoxicity on tumor cells at high concentration (≥50 µmol/L), while low concentration of resveratrol (<30 µmol/L) increased the cell viability. The principal effect of resveratrol and piceid on the viability of tumor cells was caused by the cell cycle arrest, while the effect on apoptosis was relatively minor. The reason that piceid showed lower biological activity than resveratrol at the same concentration was probably because piceid was more difficult in being uptaken by cells.

Objective:To compare the scavenging hydroxyl free radical activity and the effect of resveratrol and polydatin on hydrogen peroxide induced oxidative human umbilical vein endothelium cell(ECV304) damage.Method:Phenanthroline-Fe~(2+) method were used to evaluate the scavenging hydroxyl free radical activity of resveratrol and polydatin.Cultured ECV304 were injured by hydrogen peroxide.Cell viability was measured by MTT assay.Result:The scavenging hydroxyl free radical abilities of resveratrol and polydatin were increased in dose-dependent manner.Compared with VC,the scavenging effects of resveratrol and polydatin were weaker than it. While,the scavenging effect of polydatin on hydroxyl free radical was stronger than that of resveratrol.On contrary,resveratrol showed more protective effect than polydatin on ECV304 cells injured by hydrogen peroxide.Conclusion:Resveratrol shows markedly protective effect on ECV304 cells injured by hydrogen peroxide.

目的:建立同时测定大鼠血浆中阿霉素和塞来昔布的液相色谱-串联质谱(LC/MS/MS)方法,研究这两种药物联合应用的药代动力学.方法:大鼠尾静脉注射阿霉素和塞来昔布,眼眶取血并抗凝,离心分离血浆,采用乙酸乙酯提取血浆中的阿霉素和塞来昔布,N2吹干乙酸乙酯,残留物用50μL甲醇溶解,取20μL用于LC/MS/MS分析.结果:用LC/MS/MS法检测大鼠血浆中阿霉素和塞来昔布的线性范围为1-800ng/mL,日内、日间精密度(RSD)均小于15%,检测血浆低、中、高三个浓度(8、50、500ng/mL)阿霉素的回收率分别为101.2%、95.1%和91.4%,检测血浆低、中、高三个浓度(8、50、500ng/mL)塞来昔布的回收率分别为105.6%、106.8%和93.7%.大鼠尾静脉注射5.8mg/kg阿霉素和3.8mg/kg塞来昔布的半衰期分别为2.3 h和3.6h,曲线下面积分别为670 ng·h·mL-1和1480ng·h·mL-1.结论:建立的方法灵敏、准确、快速,适甩于阿霉素和塞来昔布的药代动力学研究.

目的:研究用于控释体系中的可生物降解的pH敏感水凝胶的制备方法及其智能释药特性. 方法:过硫酸铵(APS)和四甲基乙二胺(TEMED)作引发体系,甲基丙烯酸缩水甘油酯(GMA)修饰的葡聚糖(GMA-dex)与丙烯酸(AAc)自由基共聚制备水凝胶. GMA-dex中GMA的取代度(DS)用核磁共振测定. 在无酶的人工胃液与人工肠液中测定凝胶的平衡溶涨率,并分别测定载有平阳霉素的水凝胶在两种释放介质中的释药曲线. 结果:GMA的取代度是10.5,凝胶在人工肠液中的溶涨率明显大于人工胃液,释放平阳霉素的速率也明显快于胃液. 24 h后,人工胃液与肠液中的累积药物释放率分别为22%和43%. 结论:聚(GMA-dex/AAc)水凝胶的溶涨与释药具有pH敏感性.