Chemistry Department, Faculty of Science, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
Clinical Pathology Department, University Hospital, Menoufia University, Shebin El-Kom 32512, Egypt.
Int J Mol Sci. 2023 Sep 14;24(18):14103. doi: 10.3390/ijms241814103.
The current study describes the encapsulation of hydroxychloroquine, widely used in traditional medicine due to its diverse pharmacological and medicinal uses, in chitosan nanoparticles (CNPs). This work aims to combine the HCQ drug with CS NPs to generate a novel nanocomposite with improved characteristics and bioavailability. HCQ@CS NPs are roughly shaped like roadways and have a smooth surface with an average size of 159.3 ± 7.1 nm, a PDI of 0.224 ± 0.101, and a zeta potential of +46.6 ± 0.8 mV. To aid in the development of pharmaceutical systems for use in cancer therapy, the binding mechanism and affinity of the interaction between HCQ and HCQ@CS NPs and BSA were examined using stopped-flow and other spectroscopic approaches, supplemented by molecular docking analysis. HCQ and HCQ@CS NPs binding with BSA is driven by a ground-state complex formation that may be accompanied by a non-radiative energy transfer process, and binding constants indicate that HCQ@CS NPs-BSA was more stable than HCQ-BSA. The stopped-flow analysis demonstrated that, in addition to increasing BSA affinity, the nanoformulation HCQ@CS NPS changes the binding process and may open new routes for interaction. Docking experiments verified the development of the HCQ-BSA complex, with HCQ binding to site I on the BSA structure, primarily with the amino acids, Thr 578, Gln 579, Gln 525, Tyr 400, and Asn 404. Furthermore, the nanoformulation HCQ@CS NPS not only increased cytotoxicity against the A549 lung cancer cell line (IC = 28.57 ± 1.72 μg/mL) compared to HCQ (102.21 ± 0.67 μg/mL), but also exhibited higher antibacterial activity against both Gram-positive and Gram-negative bacteria when compared to HCQ and chloramphenicol, which is in agreement with the binding constants. The nanoformulation developed in this study may offer a viable therapy option for A549 lung cancer.
本研究描述了羟氯喹（HCQ）的包封，由于其具有广泛的药理和药用用途，在传统医学中被广泛应用。本工作旨在将 HCQ 药物与 CS NPs 结合，生成一种具有改进特性和生物利用度的新型纳米复合材料。HCQ@CS NPs 大致呈道路状，表面光滑，平均粒径为 159.3±7.1nm，PDI 为 0.224±0.101，zeta 电位为+46.6±0.8mV。为了辅助开发用于癌症治疗的药物系统，使用停流和其他光谱方法以及分子对接分析研究了 HCQ 与 HCQ@CS NPs 和 BSA 之间相互作用的结合机制和亲和力。HCQ 和 HCQ@CS NPs 与 BSA 的结合是由基态复合物形成驱动的，可能伴随着非辐射能量转移过程，结合常数表明 HCQ@CS NPs-BSA 比 HCQ-BSA 更稳定。停流分析表明，纳米制剂 HCQ@CS NPS 除了增加 BSA 亲和力外，还改变了结合过程，并可能为相互作用开辟新途径。对接实验验证了 HCQ-BSA 复合物的形成，HCQ 与 BSA 结构上的位点 I 结合，主要与 Thr 578、Gln 579、Gln 525、Tyr 400 和 Asn 404 氨基酸结合。此外，与 HCQ（102.21±0.67μg/mL）相比，纳米制剂 HCQ@CS NPS 不仅提高了对 A549 肺癌细胞系的细胞毒性（IC=28.57±1.72μg/mL），而且与 HCQ 和氯霉素相比，对革兰氏阳性和革兰氏阴性细菌表现出更高的抗菌活性，这与结合常数一致。本研究中开发的纳米制剂可能为 A549 肺癌提供一种可行的治疗选择。
