Ultra-strong penetrating and GSH-responsive oral drug delivery system improved therapeutic effect of gemcitabine for pancreatic tumors

吉西他滨 胰腺癌 药物输送 药品 体内 生物利用度 脂质体 医学 药理学 胃肠道 化疗 癌症 内科学 纳米技术 材料科学 生物 生物技术
作者
Xu Zhang,Kejian Shi,Jiahui Mao,Ke Mao,Yangrui Jia,Jiakun Zhang,Wang Qingzhen,Ru Bai,Fene Gao,Shihui Liu,Mengyu Guo,Fenglan Qin,Shengmin Li,Chunying Chen,Huige Zhou,Jing Liu,Fulin Chen
出处
期刊:Nano Today [Elsevier]
卷期号:54: 102048-102048 被引量:1
标识
DOI:10.1016/j.nantod.2023.102048
摘要

Compared with vein injection, oral administration is a preferred non-invasive and self-help treatment option for doctors and patients for cancer therapy. However, this convenient method has been severely limited by the harsh gastrointestinal tract (GI) and various biological barriers, such as the intestinal mucus/epithelial barrier and tumor matrix barrier. Those phenomena bring a huge challenge to the stability and efficiency of the oral drug delivery system that aims to improve the therapeutic effect of chemotherapy drugs. Liposomes owning good biocompatibility are able to maintain relative stability and reduce the toxic side effects of drugs. Nevertheless, liposomes still suffer from inaccurate drug release and low drug accumulation at the focus. To overcome the above problems and obtain a more efficient drug delivery platform, we screened the length of the carbon chain and introduced the disulfide bond (-S-S-) into Cerasome to prepare Cyssome. Results of our experiments prove that Cyssome owns the siliceous bodies (-Si-O-Si-) to keep them stable in the harsh environment of the gastrointestinal tract and the appropriate Young's modulus to help them penetrate the intestinal mucus/epithelial layer, as well as the thick pancreatic cancer matrix. Meanwhile, the glutathione responsive structure in Cyssome will accelerate drug release in tumor tissues which significantly improves the bioavailability of gemcitabine and reduces the related side effects. The anticancer experiments on the pancreatic cancer model in vitro and in vivo prove that Cyssome takes great potential in comprehensively improving the efficacy of oral medication for pancreatic cancer.
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