Nabipour Hafezeh, Aliakbari Farhang, Volkening Kathryn, Strong Michael J, Rohani Sohrab
Department of Chemical and Biochemical Engineering, University of Western Ontario, London, ON N6A 5B9, Canada.
Molecular Medicine Group, Robarts Research Institute, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada; Department of Bioprocess Engineering, National Institute of Genetic Engineering and Biotechnology, Tehran, Iran.
Int J Biol Macromol. 2025 Feb;291:138878. doi: 10.1016/j.ijbiomac.2024.138878. Epub 2024 Dec 17.
In modern times, achieving precise drug delivery through a safe and stable carrier remains a significant challenge. In this study, we synthesized a novel ligand based on a guanazole Schiff base and subsequently developed new metal-organic framework (MOF) named UWO-1 through a reaction involving zinc acetate. At the same time, curcumin (CUR) was loaded onto the newly synthesized UWO-1. The formation of UWO-1 and CUR loading were confirmed through various spectral analyses, including FT-IR, SEM, PXRD, XPS, TGA, zeta potential, DLS, and BET. The specific BET surface area of the UWO-1 is approximately 1456.50 m/g. The resulting drug delivery system exhibited a drug loading of 30.7 % and an encapsulation efficiency of 94.9 %. CUR@UWO-1 demonstrated rapid drug release, leading to the application of a chitosan (CS) coating to achieve controlled and delayed intravenous delivery, resulting in the creation of CS/CUR@UWO-1 biocomposite microspheres. The cumulative release profile of CUR from CS/CUR@UWO-1 was evaluated in phosphate-buffered saline (PBS) at pH 5.0 and 7.4 over 18 h, revealing release percentages of 66.99 % and 47.18 %, respectively. The release kinetics were studied and found to closely follow the Higuchi model, which was determined to be the best fit. Furthermore, the material's cytotoxicity and anticancer activity were assessed by measuring mitochondrial metabolic activity in vitro. Additionally, this nanosystem was able to internalize the drug into the cells. The combined advantages of enhanced drug loading and sustained pH-responsive release highlight the potential of the MOF-based biocomposite as a versatile drug delivery system for therapeutic applications.
在现代，通过安全稳定的载体实现精确给药仍然是一项重大挑战。在本研究中，我们基于胍唑席夫碱合成了一种新型配体，随后通过醋酸锌参与的反应开发了名为UWO-1的新型金属有机框架（MOF）。同时，将姜黄素（CUR）负载到新合成的UWO-1上。通过包括傅里叶变换红外光谱（FT-IR）、扫描电子显微镜（SEM）、粉末X射线衍射（PXRD）、X射线光电子能谱（XPS）、热重分析（TGA）、zeta电位、动态光散射（DLS）和比表面积分析（BET）等各种光谱分析确认了UWO-1的形成和CUR的负载。UWO-1的比表面积约为1456.50 m/g。所得的给药系统表现出30.7%的载药量和94.9%的包封率。CUR@UWO-1表现出快速的药物释放，因此应用壳聚糖（CS）涂层以实现可控和延迟的静脉给药，从而制备了CS/CUR@UWO-1生物复合微球。在pH 5.0和7.4的磷酸盐缓冲盐水（PBS）中对CS/CUR@UWO-1中CUR的累积释放曲线进行了18小时的评估，结果显示释放百分比分别为66.99%和47.18%。对释放动力学进行了研究，发现其紧密遵循Higuchi模型，该模型被确定为最佳拟合。此外，通过体外测量线粒体代谢活性评估了该材料的细胞毒性和抗癌活性。此外，该纳米系统能够将药物内化到细胞中。增强的载药量和持续的pH响应释放的综合优势突出了基于MOF的生物复合材料作为用于治疗应用的通用给药系统的潜力。
