Bagherifam Shahla, Skjeldal Frode Miltzow, Griffiths Gareth, Mælandsmo Gunhild M, Engebråten Olav, Nyström Bo, Hasirci Vasif, Hasirci Nesrin
Graduate Department of Polymer Science and Technology, Middle East Technical University, Ankara, Turkey.
Pharm Res. 2015 Apr;32(4):1249-63. doi: 10.1007/s11095-014-1530-0. Epub 2014 Oct 7.
The aim of this study was to design stimuli-responsive nanocarriers for anti-cancer drug delivery. For this purpose, doxorubicin (DOX)-loaded, polysebacic anhydride (PSA) based nanocapsules (NC) were combined with pH-sensitive poly (L-histidine) (PLH).
PSA nano-carriers were first loaded with DOX and were coated with poly L-histidine to introduce pH sensitivity. The PLH-coated NCs were then covered with polyethylene glycol (PEG) to reduce macrophage uptake. The drug release profile from this system was examined in two different buffer solutions prepared as acidic (pH5) and physiological (pH 7.4) media. The physical and chemical properties of the nanocapsules were characterized by Fourier transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), ultraviolet and visible absorption spectroscopy (UV-VIS), and scanning electron microscopy (SEM). In vitro studies of the prepared nanocapsules were conducted in MDA-MB-231 breast cancer cells.
The results obtained by SEM and DLS revealed that nanocapsules have spherical morphology with an average size of 230 nm. Prepared pH sensitive nanocapsules exhibited pH-dependent drug release profile and promising intracellular release of drug. PEGylation of nanoparticles significantly prevented macrophage uptake compared to non-PEGylated particles.
本研究的目的是设计用于抗癌药物递送的刺激响应性纳米载体。为此,将负载阿霉素(DOX)的聚癸二酸酐(PSA)基纳米胶囊(NC)与pH敏感的聚(L-组氨酸)(PLH)相结合。
首先将DOX负载到PSA纳米载体上,并用聚L-组氨酸包被以引入pH敏感性。然后用聚乙二醇(PEG)覆盖PLH包被的NCs以减少巨噬细胞摄取。在制备的酸性(pH5)和生理(pH 7.4)介质的两种不同缓冲溶液中检查该系统的药物释放曲线。通过傅里叶变换红外光谱(FTIR)、动态光散射(DLS)、紫外可见吸收光谱(UV-VIS)和扫描电子显微镜(SEM)对纳米胶囊的物理和化学性质进行表征。在MDA-MB-231乳腺癌细胞中对制备的纳米胶囊进行体外研究。
SEM和DLS获得的结果表明,纳米胶囊具有球形形态,平均尺寸为230nm。制备的pH敏感纳米胶囊表现出pH依赖性药物释放曲线和有前景的药物细胞内释放。与未聚乙二醇化的颗粒相比,纳米颗粒的聚乙二醇化显著防止了巨噬细胞摄取。