Instituto de Química de São Carlos, Universidade de São Paulo, Caixa Postal 780, 13560-970 São Carlos, SP, Brazil; Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossgarten 3, Münster 48149, Germany.
Institute of Plant Biology and Biotechnology (IBBP), Westfälische Wilhelms-Universität Münster, Schlossgarten 3, Münster 48149, Germany.
Eur J Pharm Biopharm. 2018 Oct;131:203-210. doi: 10.1016/j.ejpb.2018.08.009. Epub 2018 Aug 23.
Novel drug delivery strategies are needed to meet the complex challenges associated to cancer therapy. Biocompatible pH-sensitive drug delivery nanocarriers based on amphiphilic co-polymers seem to be promising for cancer treatment. In the present study, a drug delivery system was produced by encapsulating quercetin into novel pH-sensitive self-assembled amphiphilic chitosan nanoparticles. Up to 83% of quercetin was entrapped by the nanoparticles. The particle diameter, as measured by dynamic light scattering (DLS), ranged from ∼235 to ∼312 nm for the blank and ∼490 to ∼502 nm for the loaded carriers. The results showed that the payload release is larger at acidic pH (5.0) than at physiological pH (7.4). Fitting the data to the Korsmeyer-Peppas model indicated that anomalous diffusion is the predominant release mechanism at pH 5.0, while Fickian diffusion operates at pH 7.4. The MTT assay revealed that blank nanoparticles were non-antiproliferative for the cell tested. The results further revealed that quercetin maintains its metabolism inhibition against MCF-7 cells after encapsulation. Cellular uptake experiments showed that nanoparticles accumulated on the cell surface, whereas few were internalized. Haemocompatibility test results suggest that the nanoparticles exhibit suitable blood compatibility for biological applications. Results suggest that nanoparticles might be a promising pH-sensitive drug delivery system for applications in anticancer treatment.
需要新的药物传递策略来应对与癌症治疗相关的复杂挑战。基于两亲共聚物的生物相容的 pH 敏感药物传递纳米载体似乎是癌症治疗的有前途的选择。在本研究中，通过将槲皮素包封到新型 pH 敏感自组装两亲壳聚糖纳米粒子中，制备了一种药物传递系统。多达 83%的槲皮素被纳米粒子包封。通过动态光散射（DLS）测量的粒径，对于空白纳米粒子在 235 至 312nm 之间变化，而对于负载载体在 490 至 502nm 之间变化。结果表明，在酸性 pH（5.0）下的载药量释放大于生理 pH（7.4）。将数据拟合到 Korsmeyer-Peppas 模型表明，在 pH 5.0 下，异常扩散是主要的释放机制，而在 pH 7.4 下，Fickian 扩散起作用。MTT 测定表明空白纳米粒子对测试的细胞没有抗增殖作用。结果进一步表明，槲皮素在包封后仍然保持对 MCF-7 细胞的代谢抑制作用。细胞摄取实验表明，纳米粒子积聚在细胞表面，而很少被内化。血液相容性测试结果表明，纳米粒子对生物应用具有合适的血液相容性。结果表明，纳米粒子可能是一种有前途的 pH 敏感药物传递系统，可应用于癌症治疗。
