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纳米国会2019年释放阿霉素的体外研究微凝胶和其他两亲性药物:改善机械的理解——每Hansson-Uppsala大学

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抽象阿霉素的释放率(阿霉素)的药物传输系统(DDS)、直流珠,研究了by2小型化体外方法:free-i¬‚由于水库和示例。体外释放机制系统的依赖条件进行了实验和理论建模。之间的反比关系被发现释放率和珠大小,一大部分原因要归咎于总表面积就越大。释放率与温度相关积极,释放介质体积,和缓冲力量,虽然释放介质体积比缓冲强度有较大的影响。样品储层方法生成的释放速度变慢,这描述了体内释放proi¬le更准确地比free-i¬‚由于方法。没有区别pH值6.3或7.4的租赁利率,这意味着微酸性tum或微环境对药物释放更少的重要性。搅拌速率和释放速率之间的正相关关系观察DDS大小,这表明我¬lm控制释放。理论模型强调了ini¬‚元代的当地的质子化作用的平衡,self-aggregation和阿霉素的珠子材料交互作用。释放的理论模型可以描述观察到的更大的敏感性的释放率释放介质的体积相比缓冲力量。小型化体外的组合方法和theoreticalmodeling是有用的识别的重要参数和流程从微凝胶DDS阿霉素的释放。介绍体外药物释放药物传输系统(DDS)的调查的重要性在药物创新和开发过程。1然而,不存在标准化的体外方法使用系统,作为一个结果,有逆境的体外方法。 The in vitro release rate of doxorubicin (DOX) from the microsphere DDS, DC Bead, has been investigated in paddle, sample and separate, flow through, and T-cell methods. These in vitro methods use relatively large amounts of DDS (1 mL) and release medium (200-900 ml). Miniaturized in vitro methods reduce the amounts of DDS sample, release medium and waste for example, to 20-65mL (DDS sample) and 10-20 mL (release medium). Another advantage of the miniaturized method is that a low volume of release medium may be more relevant to the in vivo site in hydrodynamic and diffusion properties.In this report, the in vitro release of DOX from the beads was tested in 2 miniaturized methods. The beads were loaded with DOX, a cytotoxic agent that is used in palliative treatment of intermediate-stage hepatocellular carcinoma. DOX has a molecular mass of 543.52 g/mol and a LogD7.5of2.42. The pK as of DOX are 7.34, 8.46, and 9.46, and the compound exists as both a deprotonated and protonated monovalent cation at physiological conditions. The beads consist of polyvinyl alcohol (PVA) with integrated, negatively charged 2-acrylamido-2-methylpropanesulfonate (AMPS) units. Ion exchange has been proposed as the mechanism for loading and release of protonated DOX from the AMPS sulfonic acid groups. The beads are no biodegradable, and the intrahepatic administration leads to a local drug delivery in combination with a full and permanent embolization of the treated hepatic arteries. In the clinic, the beads are delivered by radiological image guidance with anon ionic contrast medium, such as Omnipaque. The main objective of this study was to determine the mechanism(s) and release rate of DOX from the beads. Second, we investigated the effects of factors such as temperature, stir-ring rates, buffer strength, pH, and volume of release medium on the in vitro release rate. Third, selected in vitro release profileswere compared to an in vivo DOX-release data set. Finally, the release mechanism(s) were investigated with theoretical modeling. Experimental Design Am Diss profiler (pION) was used to determine the in vitro DOX release from the beads during various conditions. The drug concentration in the medium was determined as the area under the concentration wavelength curve of the second derivate spectrum at an interval of 553 to 572 nm. The application of the second derivate spectrum reduces the background turbidity, thereby enhancing peaks and reducing baseline shifting.21, 22Each channel was individually calibrated with the stock solutions against a standard curve. All release studies were per-formed under sink conditions (amount of DOX Per Hansson

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