Department of Biotechnology, Faculty of Advanced Sciences and Technologies, University of Isfahan, Isfahan, Iran.
Department of Chemistry and Bioscience, Faculty of Chemistry, Aalborg University, Aalborg, Denmark.
Int J Nanomedicine. 2019 Aug 30;14:7017-7038. doi: 10.2147/IJN.S221598. eCollection 2019.
Fabrication of a smart drug delivery system that could dramatically increase the efficiency of chemotherapeutic drugs and reduce the side effects is still a challenge for pharmaceutical researchers. By the emergence of nanotechnology, a huge window was opened towards this goal, and a wide type of nanocarriers were introduced for delivering the chemotherapeutic to the cancer cells, among them are cyclodextrins with the ability to host different types of hydrophobic bioactive molecules through inclusion complexation process.
The aim of this study is to design and fabricate a pH-responsive theranostic nanocapsule based on cyclodextrin supramolecular nano-structure.
This nanostructure contains iron oxide nanoparticles in the core surrounded with three polymeric layers including polymeric β-cyclodextrin, polyacrylic acid conjugated to sulfadiazine, and polyethylenimine functionalized with β-cyclodextrin. Sulfadiazine is a pH-responsive hydrophobic component capable of making inclusion complex with β-cyclodextrin available in the first and third layers. Doxorubicin, as an anti-cancer drug model, was chosen and the drug loading and release pattern were determined at normal and acidic pH. Moreover, the biocompatibility of the nanocapsule (with/without drug component) was examined using different techniques such as MTT assay, complement activation, coagulation assay, and hemolysis.
The results revealed the successful preparation of a spherical nanocapsule with mean size 43±1.5 nm and negatively charge of -43 mV that show 160% loading efficacy. Moreover, the nanocapsule has an on/off switching release pattern in response to pH that leads to drug released in low acidic pH. The results of the biocompatibility tests indicated that this nano drug delivery system had no effect on blood and immune components while it could affect cancer cells even at very low concentrations (0.3 μg mL).
The obtained results suggest that this is a "switchable" theranostic nanocapsule with potential application as an ideal delivery system for simultaneous cancer diagnosis and therapy.
开发一种能够显著提高化疗药物效率并降低副作用的智能药物输送系统仍然是制药研究人员面临的挑战。随着纳米技术的出现，为实现这一目标开辟了巨大的窗口，并且引入了广泛类型的纳米载体来将化疗药物递送到癌细胞中，其中包括能够通过包合络合过程容纳不同类型疏水性生物活性分子的环糊精。
本研究旨在设计和制备基于环糊精超分子纳米结构的 pH 响应治疗性纳米胶囊。
这种纳米结构包含内核中的氧化铁纳米粒子，被三层聚合物包围，包括聚合物β-环糊精、与磺胺嘧啶偶联的聚丙烯酸和β-环糊精官能化的聚亚乙基亚胺。磺胺嘧啶是一种 pH 响应的疏水性成分，能够与第一层和第三层中环糊精形成包合物。选择阿霉素作为抗癌药物模型，在正常和酸性 pH 下测定药物的载药量和释放模式。此外，还使用 MTT 测定法、补体激活、凝血测定和溶血等不同技术来检测纳米胶囊（有/无药物成分）的生物相容性。
结果表明成功制备了一种平均粒径为 43±1.5nm 的球形纳米胶囊，其带负电荷为-43mV，载药效率为 160%。此外，纳米胶囊在 pH 响应下具有开/关释放模式，导致药物在低酸性 pH 下释放。生物相容性测试结果表明，这种纳米药物输送系统对血液和免疫成分没有影响，而即使在非常低的浓度（0.3μg mL）下也会影响癌细胞。
研究结果表明，这是一种具有潜在应用价值的“可切换”治疗性纳米胶囊，可作为同时进行癌症诊断和治疗的理想药物输送系统。
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