Research Centre for Pharmaceutical Nanotechnology, Tabriz University of Medical Sciences, Tabriz, Iran.
Chemical Engineering Faculty, Sahand University of Technology, Sahand New Town, Tabriz, Iran.
Oxid Med Cell Longev. 2022 Sep 19;2022:1548410. doi: 10.1155/2022/1548410. eCollection 2022.
In this study, to reduce the side effects of anticancer drugs and also to increase the efficiency of current drug delivery systems, a pH and temperature-responsive polymeric nanogel was synthesized by copolymerization of N-vinylcaprolactam (VCL) and acrylic acid (AA) monomers (P(VCL-co-AA)) with a novel cross-linker, triethylene glycol dimethacrylate (TEGDMA), as a biocompatible and nontoxic component. The structural and physicochemical features of the P(VCL-co-AA) nanogel were characterized by FT-IR, DLS/Zeta potential, FE-SEM, and HNMR techniques. The results indicated that spherical polymeric nanogel was successfully synthesized with a 182 nm diameter. The results showed that the polymerization process continues with the opening of the carbon-carbon double bond of monomers, which was approved by C-C band removing located at 1600 cm. Doxorubicin (Dox) as a chemotherapeutic agent was loaded into the P(VCL-co-AA), whit a significant loading of Dox (83%), and the drug release profile was investigated in the physiological and cancerous site simulated conditions. P(VCL-co-AA) exhibited a pH and temperature-responsive behavior, with an enhanced release rate in the cancerous site condition. The biocompatibility and nontoxicity of P(VCL-co-AA) were approved by MTT assay on the normal human foreskin fibroblasts-2 (HFF-2) cell line. Also, Dox-loaded P(VCL-co-AA) had excellent toxic behavior on the Michigan Cancer Foundation-7 (MCF-7) cell line as model cancerous cells. Moreover, Dox-loaded P(VCL-co-AA) had higher toxicity in comparison with free Dox, which would be a vast advantage in reducing Dox side effects in the clinical cancer treatment applications.
在这项研究中,为了降低抗癌药物的副作用,并提高当前药物输送系统的效率,通过共聚 N-乙烯基己内酰胺(VCL)和丙烯酸(AA)单体(P(VCL-co-AA))与一种新型交联剂三甘醇二甲基丙烯酸酯(TEGDMA)合成了一种 pH 和温度响应性的聚合物纳米凝胶,作为一种生物相容性和无毒的成分。通过傅里叶变换红外光谱(FT-IR)、动态光散射/ζ 电位、FE-SEM 和 HNMR 技术对 P(VCL-co-AA)纳米凝胶的结构和物理化学特性进行了表征。结果表明,成功合成了直径为 182nm 的球形聚合物纳米凝胶。结果表明,聚合过程是通过单体的碳-碳双键的打开继续进行的,这得到了位于 1600cm 处的 C-C 带去除的证实。阿霉素(Dox)作为一种化疗药物被载入 P(VCL-co-AA)中,Dox 的载药量高达 83%,并在生理和癌症部位模拟条件下研究了药物释放情况。P(VCL-co-AA)表现出 pH 和温度响应行为,在癌症部位条件下释放速率增强。MTT 测定法在正常人包皮成纤维细胞-2(HFF-2)细胞系上证实了 P(VCL-co-AA)的生物相容性和低毒性。此外,作为模型癌细胞的密歇根癌症基金会-7(MCF-7)细胞系上负载 Dox 的 P(VCL-co-AA)具有优异的毒性行为。而且,负载 Dox 的 P(VCL-co-AA)的毒性比游离 Dox 更高,这将在减少临床癌症治疗应用中 Dox 的副作用方面具有巨大优势。