Middle East Technical University, Department of Biotechnology, Ankara, 06800, Turkey.
Middle East Technical University, Central Laboratory, Molecular Biology and Biotechnology R&D Center, Ankara, 06800, Turkey.
J Pharm Sci. 2013 Jun;102(6):1825-1835. doi: 10.1002/jps.23524. Epub 2013 Apr 5.
Nanotechnology is a promising alternative to overcome the limitations of classical chemotherapy. As a novel approach, dendrimer-coated magnetic nanoparticles (DcMNPs) maintain suitable drug delivery system because of their buildup of functional groups, symmetry perfection, nanosize, and internal cavities. They can also be targeted to the tumor site in a magnetic field. The aim of this study is to obtain an effective targeted delivery system for doxorubicin, using polyamidoamine (PAMAM) DcMNPs. Different generations (G2 , G3 , G4 , and G7 ) of PAMAM DcMNPs were synthesized. Doxorubicin loading, release, and stability efficiencies in these nanoparticles (NPs) were studied. The results showed that low-generation NPs obtained in this study have pH-sensitive drug release characteristics. G4 DcMNP, which releases most of the drug in lower pH, seems to be the most suitable generation for efficient Doxorubicin delivery. Furthermore, application of doxorubicin-loaded G4 DcMNPs may help to overcome doxorubicin resistance in MCF-7 cells. On the contrary, G2 and G3 DcMNPs would be suitable for the delivery of drugs such as vinca alkaloids (Johnson IS, Armstrong JG, Gorman M, Burnett JP. 1963. Cancer Res 23:1390-1427.) and taxenes (Clarke SJ, Rivory LP. 1999. Clin Pharmacokinet 36(2):99-114.), which show their effects in cytoplasm. The results of this study can provide new insights in the development of pH-sensitive targeted drug delivery systems to overcome drug resistance during cancer therapy.
纳米技术是克服经典化疗局限性的一种有前途的替代方法。作为一种新方法，树枝状大分子包裹的磁性纳米粒子（DcMNPs）由于其具有的官能团、对称性、纳米尺寸和内部空腔而保持合适的药物传递系统。它们还可以在磁场中靶向肿瘤部位。本研究的目的是获得一种有效的多柔比星靶向递药系统，使用聚酰胺-胺（PAMAM）DcMNPs。合成了不同代数（G2、G3、G4 和 G7）的 PAMAM DcMNPs。研究了这些纳米粒子（NPs）中阿霉素的负载、释放和稳定性效率。结果表明，本研究中获得的低代 NPs 具有 pH 敏感的药物释放特性。在较低 pH 值下释放大部分药物的 G4 DcMNP 似乎是最适合有效递送多柔比星的代。此外，载多柔比星 G4 DcMNPs 的应用可能有助于克服 MCF-7 细胞中的多柔比星耐药性。相反，G2 和 G3 DcMNPs 适合递送长春花生物碱（Johnson IS，Armstrong JG，Gorman M，Burnett JP. 1963. Cancer Res 23:1390-1427.）和紫杉烷类药物（Clarke SJ，Rivory LP. 1999. Clin Pharmacokinet 36(2):99-114.），它们在细胞质中发挥作用。本研究的结果可为开发 pH 敏感的靶向药物传递系统提供新的见解，以克服癌症治疗过程中的药物耐药性。
