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用于癌症有效联合治疗的西他列汀-木质素聚合物药物递送系统包裹的阿霉素

Doxorubicin encapsulated blend of sitagliptin-lignin polymeric drug delivery system for effective combination therapy against cancer.

作者信息

Liaqat Sana, Fatima Batool, Hussain Dilshad, Imran Muhammad, Zahra Jawad Shan E, Imran Muhammad, Saeed Adeela, Majeed Saadat, Najam-Ul-Haq Muhammad

机构信息

Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan.

Department of Biochemistry, Bahauddin Zakariya University, Multan 60800, Pakistan.

出版信息

Int J Biol Macromol. 2024 Jun;269(Pt 2):132146. doi: 10.1016/j.ijbiomac.2024.132146. Epub 2024 May 9.

Abstract

In this research, a sitagliptin-lignin biopolymer (SL) containing zinc selenide quantum dots (ZnSe QDs) and doxorubicin (doxo) was synthesized. The fabricated polymeric drug delivery system was characterized via FTIR, XRD, SEM, TGA, IR, and DSC. SLQD-Doxo exhibited an irregular surface with a 32 nm diameter and well-defined surface chemistry. Drug loading efficiency was assessed at different concentrations, pH levels, time intervals, and temperatures, and drug kinetics were calculated. Maximum drug release was observed at 6 μmol concentration after 24 h, pH of 6.5 and 45 °C. The maximum drug encapsulation efficiency was 81.75 %. SLQD-Doxo demonstrated 24.4 ± 1.04 % anti-inflammatory activity, and the maximum lipoxygenase inhibition in a concentration-dependent manner was 71.45 ± 2.02 %, compared to indomethacin, a standard anticancer drug. The designed system was applied to breast cancer MCF-7 cells to evaluate anticancer activity. Cytotoxicity of SLQD-Doxo resulted in 24.48 ± 1.64 dead cells and 74.39 ± 4.12 viable cells. Lignin's polyphenolic nature resulted in good antioxidant activity of LLQD-Doxo. The combination of SLQD-Doxo was appropriate for drug delivery at high temperatures and acidic pH of tumor cells compared to healthy cells.

摘要

在本研究中,合成了一种包含硒化锌量子点(ZnSe QDs)和阿霉素(doxo)的西他列汀-木质素生物聚合物(SL)。通过傅里叶变换红外光谱(FTIR)、X射线衍射(XRD)、扫描电子显微镜(SEM)、热重分析(TGA)、红外光谱(IR)和差示扫描量热法(DSC)对制备的聚合物药物递送系统进行了表征。SLQD-Doxo呈现出不规则表面,直径为32 nm,表面化学性质明确。在不同浓度、pH值、时间间隔和温度下评估了药物负载效率,并计算了药物动力学。在24小时后,6 μmol浓度、pH值为6.5和45°C的条件下观察到最大药物释放。最大药物包封效率为81.75%。与标准抗癌药物吲哚美辛相比,SLQD-Doxo表现出24.4±1.04%的抗炎活性,以浓度依赖性方式的最大脂氧合酶抑制率为71.45±2.02%。将设计的系统应用于乳腺癌MCF-7细胞以评估其抗癌活性。SLQD-Doxo的细胞毒性导致24.48±1.64个死细胞和74.39±4.12个活细胞。木质素的多酚性质导致LLQD-Doxo具有良好的抗氧化活性。与健康细胞相比,SLQD-Doxo的组合适合在高温和肿瘤细胞的酸性pH值下进行药物递送。

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