Department of Endodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, People's Republic of China.
Department of Prosthodontics, The Affiliated Stomatological Hospital of Nanjing Medical University, State Key Laboratory Cultivation Base of Research, Prevention and Treatment for Oral Diseases, Jiangsu Province Engineering Research Center of Stomatological Translational Medicine, Nanjing, 210029, People's Republic of China.
Int J Nanomedicine. 2024 Nov 9;19:11577-11592. doi: 10.2147/IJN.S485581. eCollection 2024.
Based on nanomedicine strategies, this study employed cucurbit[7]uril (Q[7]) as the macromolecular carrier to synthesize nanocomplex drug delivery system for chlorogenic acid (CGA). The nanocomplex drug delivery system is intended to overcome the unsatisfactory biocompatibility and bioavailability of CGA and realizing its potential role in long-term osteoporosis (OP) medication.
The nanocomplex was synthesized by the reflux stirring method. The chemical structure of the nanocomplex was characterized by Fourier transform infrared spectroscopy (FTIR), thermogravimetric analysis (TGA), X-ray diffraction analysis (XRD), UV-visible spectrophotometry (UV-vis), zeta potential analysis and transmission electronic microscope (TEM). The Cell Counting Kit-8 (CCK-8) assay, Live/Dead staining assay, and cytoskeleton staining were conducted to testify the biocompatibility of the nanocomplex. The release assay, Ferric Reducing Ability of Plasma (Frap) assay and Reactive oxygen species (ROS) staining were implemented to evaluate the release profile of CGA as well as its remaining antioxidative levels.
CGA and Q[7] formed hydrogen bonding through an exclusion interaction, with the binding ratio more than 1:1. The nanocomplex had a crystalline and spherical-like structure and improved thermal stability. The nanocomplex demonstrated better biocompatibility than free CGA. The release profile of CGA from the nanocomplex was much steadier, and 70% of CGA was released in 5 days. The CGA released from the nanocomplex maintained its antioxidative properties at high levels and effectively eliminated the accumulated ROS in MC3T3-E1 cells under oxidative stress.
Q[7] has been demonstrated to be an ideal nanocarrier for CGA and the nanocomplex delivery system holds the potential for the long-term medication strategy of OP.
本研究基于纳米医学策略，采用葫芦[7]脲（Q[7]）作为大分子载体，合成了绿原酸（CGA）的纳米复合药物传递系统。该纳米复合药物传递系统旨在克服 CGA 不理想的生物相容性和生物利用度，实现其在长期骨质疏松症（OP）药物治疗中的潜在作用。
采用回流搅拌法合成纳米复合物。采用傅里叶变换红外光谱（FTIR）、热重分析（TGA）、X 射线衍射分析（XRD）、紫外可见分光光度法（UV-vis）、Zeta 电位分析和透射电子显微镜（TEM）对纳米复合物的化学结构进行了表征。采用细胞计数试剂盒-8（CCK-8）测定法、Live/Dead 染色测定法和细胞骨架染色法验证纳米复合物的生物相容性。进行释放测定、血浆铁还原能力（Frap）测定和活性氧（ROS）染色，评估 CGA 的释放特性及其剩余抗氧化水平。
CGA 和 Q[7]通过排除相互作用形成氢键，结合比大于 1:1。纳米复合物具有结晶和类球形结构，热稳定性提高。纳米复合物比游离 CGA 具有更好的生物相容性。CGA 从纳米复合物中的释放曲线更加稳定，5 天内释放了 70%的 CGA。从纳米复合物中释放的 CGA 保持了高水平的抗氧化特性，并在氧化应激下有效消除了 MC3T3-E1 细胞中积累的 ROS。
Q[7]已被证明是 CGA 的理想纳米载体，纳米复合物给药系统有望成为 OP 长期药物治疗策略的候选药物。
