Department of Pharmaceutical Technology, Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand; Pharmaceutical Biopolymer Group (PBiG), Faculty of Pharmacy, Silpakorn University, Nakhon Pathom 73000, Thailand.
School of Pharmacy, Faculty of Health Sciences, Curtin University, Perth 6845, Australia; Curtin Health Innovation Research Institute of Ageing and Chronic Disease, Bentley 6102, Australia.
Carbohydr Polym. 2015 Aug 1;126:222-30. doi: 10.1016/j.carbpol.2015.03.018. Epub 2015 Mar 18.
Efficacy of doxorubicin (DOX) in colorectal cancer treatment is limited by undesirable side-effects, which are partially due to nonspecific delivery DOX to the tumor target site. This study aimed to develop pH-responsive dextrin nanogels (DNGs) as anticancer drug carriers with pH-controlled drug release. DNGs prepared with formaldehyde as a cross-linker (FDNGs) exhibited smaller size, compared to that using glyoxal (GDNGs). Both DNGs showed pH-dependent drug release properties; drug release was slow at neutral pH but increased significantly in acidic medium. The cytotoxicity of empty and DOX-loaded FDNGs was lower than free DOX and GDNGs, against two commonly used colorectal cancer cells. Intracellular uptake studies indicated that the DOX-loaded FDNGs could efficiently deliver DOX into the nuclei. In vivo, DOX-loaded FDNGs substantially enhanced anti-tumor efficacy, compared to free DOX, exhibiting much higher effects on inhibiting proliferation and inducing apoptosis, as confirmed by mice weight shifts, tumor weight, tumor volume and histological assessment. Therefore, FDNGs are promising as a potential drug delivery vehicle for colorectal cancer therapy.
阿霉素（DOX）在结直肠癌治疗中的疗效受到不良副作用的限制，这些副作用部分是由于 DOX 不能特异性地递送到肿瘤靶位。本研究旨在开发 pH 响应性糊精纳米凝胶（DNGs）作为具有 pH 控制药物释放的抗癌药物载体。用甲醛作为交联剂（FDNGs）制备的 DNGs 与使用乙二醛（GDNGs）相比，粒径更小。两种 DNGs 均表现出 pH 依赖性药物释放特性；在中性 pH 下药物释放缓慢，但在酸性介质中显著增加。载有空药和 DOX 的 FDNGs 的细胞毒性低于游离 DOX 和 GDNGs，对两种常用的结直肠癌细胞均有效。细胞内摄取研究表明，DOX 载药 FDNGs 可以有效地将 DOX 递送到细胞核内。在体内，与游离 DOX 相比，载 DOX 的 FDNGs 显著增强了抗肿瘤疗效，通过小鼠体重变化、肿瘤重量、肿瘤体积和组织学评估，证实了其对抑制增殖和诱导凋亡的作用更高。因此，FDNGs 有望成为结直肠癌治疗的潜在药物递送载体。
