Kru Kle-Be Rziṇa Kristi Ne, Lends Alons, Boguszewska-Czubara Anna
Latvian Institute of Organic Synthesis, Aizkraukles iela 21, Riga LV-1006, Latvia.
Department of Medical Chemistry, Medical University of Lublin, Chodzki 4A, Lublin 20-093, Poland.
ACS Omega. 2024 Feb 12;9(8):8874-8884. doi: 10.1021/acsomega.3c06745. eCollection 2024 Feb 27.
The cyclodextrin-based metal-organic frameworks (CD MOFs) are a suitable molecular platform for drug delivery systems of various active pharmaceutical ingredients (APIs). The low toxicity and cost-efficient synthesis make CD MOFs an attractive host for the encapsulation of APIs. In this study, we created a model system based on γCD-K MOFs with widely used drugs carmofur (HCFU), 5-fluorouracil (5-FU), and salicylic acid (HBA) to study host-guest encapsulation methods using different crystallization protocols. The host-guest complexes of API:CD MOF in an in-depth study were investigated by liquid chromatography-mass spectrometry (LC-MS), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and F- and C-detected solid-state NMR spectroscopy (ssNMR). These techniques confirmed the structure and interaction sites within the encapsulation product in the host-guest complex. We also evaluated the toxicity and biocompatibility of the API:CD MOF complex using and methods. The cytotoxicity, hepatotoxicity, and neurotoxicity were established with cell lines of fibroblasts (BJ), human liver cell line (HepG2), and human oligodendrocytic cells (MO3.13). Then, was used as an experimental model of ecotoxicity. The results showed the choice of γCD-K-5 as the most protective and safe option for drug encapsulation to decrease its toxicity level against normal cells.
基于环糊精的金属有机框架(CD MOFs)是用于各种活性药物成分(APIs)药物递送系统的合适分子平台。低毒性和成本效益高的合成方法使CD MOFs成为封装APIs的有吸引力的主体。在本研究中,我们创建了一个基于γCD-K MOFs与广泛使用的药物卡莫氟(HCFU)、5-氟尿嘧啶(5-FU)和水杨酸(HBA)的模型系统,以研究使用不同结晶方案的主客体封装方法。通过液相色谱-质谱联用(LC-MS)、差示扫描量热法(DSC)、热重分析(TGA)以及F和C检测的固态核磁共振光谱(ssNMR)对深入研究的API:CD MOF主客体复合物进行了研究。这些技术证实了主客体复合物中封装产物的结构和相互作用位点。我们还使用[具体方法1]和[具体方法2]评估了API:CD MOF复合物的毒性和生物相容性。用成纤维细胞系(BJ)、人肝癌细胞系(HepG2)和人少突胶质细胞系(MO3.13)确定了细胞毒性、肝毒性和神经毒性。然后,[具体生物]被用作生态毒性的实验模型。结果表明,选择γCD-K-5作为药物封装最具保护性和安全性的选择,可降低其对正常细胞的毒性水平。