a School of Chemistry & Materials Science , Jiangsu Key Laboratory of Green Synthetic Chemistry for Functional Materials, Jiangsu Normal University , Xuzhou , China.
b Orthopaedic Institute, Medical College , Soochow University , Suzhou , China.
Drug Deliv. 2019 Dec;26(1):300-308. doi: 10.1080/10717544.2019.1580323.
We describe a biodegradable amphiphilic polyurethane (PU) with disulfide bonds in the main chain [PEtOz-b-PU(SS)-b-PEtOz]. This multi-block PU was synthesized using poly (ε-caprolactone) diol (PCL-SS-PCL) and poly (2-ethyl-2-oxazoline) (PEtOz-OH) as soft segments, and bis (2-isocyanatoethyl) disulfide as the hard segment. Acid-sensitive PEtOz-OH was used as a hydrophilic segment for pH sensitivity. And reduction sensitivity was induced via disulfide bonds incorporated into the hydrophobic poly (ε-caprolactone) segment of the amphiphilic PUs. The system can self-assemble to form micelles responsive to pH and reducing conditions. The properties of the micelle were studied with dynamic light scattering and scanning electron microscopy. Doxorubicin (DOX) was chosen as a model drug. The in vitro release studies showed that PEtOz-b-PU(SS)-b-PEtOz micelle could degrade more rapidly and completely in a reductive and acidic environment [10 mM dl-Dithiothreitol, pH 5.0]. The methyl tetrazolium (MTT) assay and fluorescent microscopy confirmed the cytotoxicity of the DOX-loaded micelles. This work provides a promising dual-responsive drug carrier based on amphiphilic PU to achieve efficient drug delivery.
我们描述了一种在主链中带有二硫键的可生物降解两亲性聚氨酯[PEtOz-b-PU(SS)-b-PEtOz]。该多嵌段 PU 是使用聚（ε-己内酯）二醇（PCL-SS-PCL）和聚（2-乙基-2-恶唑啉）（PEtOz-OH）作为软段，以及双（2-异氰酸根合乙基）二硫作为硬段合成的。酸敏感的 PEtOz-OH 被用作亲水性片段，以赋予 pH 敏感性。并且通过将二硫键引入两亲性 PU 的疏水性聚（ε-己内酯）段中，诱导了还原敏感性。该系统可以自组装形成对 pH 和还原条件有响应的胶束。通过动态光散射和扫描电子显微镜研究了胶束的性质。选择阿霉素（DOX）作为模型药物。体外释放研究表明，PEtOz-b-PU(SS)-b-PEtOz 胶束在还原和酸性环境中[10mMdl-Dithiothreitol，pH5.0]能够更快且更完全地降解。甲基噻唑基四唑（MTT）测定和荧光显微镜证实了载药胶束的细胞毒性。这项工作提供了一种有前途的基于两亲性 PU 的双重响应药物载体，以实现有效的药物传递。
