Daum Nicole, Neumeyer Andrea, Wahl Birgit, Bur Michael, Lehr Claus-Michael
Biopharmaceutics and Pharmaceutical Technology, Saarland University, Saarbruecken, Germany.
Methods Mol Biol. 2009;480:151-64. doi: 10.1007/978-1-59745-429-2_11.
Biological barriers, typically, represented by epithelial tissues are the main hindrance against uncontrolled uptake of a variety of substances. However, the delivery across a biological barrier is a crucial factor in the development of drugs. As the permeability of macromolecular drugs is very limited, new delivery strategies have to be developed and further improved. Thereby, nanoparticle carriers offer an enormous potential for the controlled delivery of active substances into the organism. Besides an intensive study for the reason of risk assessment and toxicology, the possible transport enhancement caused by nanoparticles must be quantified. A powerful tool for these studies is in vitro cell culture models imitating the more complex in vivo situation under controlled conditions. We use polyethylenimine as model enhancer mimicking toxicological effects and altered barrier function in the epithelial in vitro model, Calu-3. Cytotoxicity assays based on different mechanisms and transport properties of a low-permeability marker with and without delivery enhancer are described.
生物屏障通常由上皮组织代表，是阻止各种物质不受控制摄取的主要障碍。然而，跨越生物屏障的递送是药物开发中的关键因素。由于大分子药物的渗透性非常有限，必须开发并进一步改进新的递送策略。因此，纳米颗粒载体为将活性物质可控递送至生物体提供了巨大潜力。除了出于风险评估和毒理学原因进行深入研究外，还必须量化纳米颗粒引起的可能的转运增强。这些研究的一个强大工具是在受控条件下模拟更复杂体内情况的体外细胞培养模型。我们使用聚乙烯亚胺作为模型增强剂，在体外上皮模型Calu-3中模拟毒理学效应和改变的屏障功能。描述了基于低渗透性标记物在有和没有递送增强剂情况下的不同机制和转运特性的细胞毒性测定。
