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

Abstract

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.