Colon specific enzyme responsive oligoester crosslinked dextran nanoparticles for controlled release of 5-fluorouracil

Targeting bioactives selectively to diseased sites is one of the most challenging aspects of cancer therapy. Herein, fabrication of colonic enzyme-responsive dextran based oligoester crosslinked nanoparticles is reported for the controlled release of 5-fluorouracil (5-FU) - an anticancer drug. The 5-FU drug loaded nanoparticles (DNPs, size similar to 237 +/- 25 nm, zeta-potential -17.0 +/- 3 mV) were developed by the in-situ crosslinking of dextran with a bifunctional telechelic oligoester followed by the physical drug encapsulation via nanoprecipitation. Drug encapsulation efficiency and drug loading capacity of DNPs were found to be similar to 76% (+/- 0.1) and similar to 8% (+/- 0.1), respectively. The DNPs were demonstrated to release the encapsulated drug selectively in the presence of dextranase enzyme. The in vitro release kinetics assay revealed that the DNPs released about 75% (+/- 4) of the entrapped drug within 12 h of incubation with dextranase enzyme. No drug was released in a control experiment where DNPs were exposed to pH conditions encountered in the stomach and small intestine. Moreover, the treatment of HCT116 colon cancer cell line with the developed DNPs highlighted its biocompatibility as well as dextranase triggered cytotoxicity. The developed system offers an avenue to reduce the non-specific cytotoxicity of the encapsulated 5-FU, and a colon specific delivery of the encapsulated drug in response to the dextranase enzyme.