A dual thermo/pH-sensitive hydrogel as 5-Fluorouracil carrier for breast cancer treatment.

Abstract

Intelligent hydrogels are promising in constructing scaffolds for the controlled delivery of drugs. Here, a dual thermo- and pH-responsive hydrogel called PCG [poly ( N -isopropyl acrylamide-co-itaconic acid)/chitosan/glycerophosphate (PNI/CS/GP)] was established as the carrier of 5-fluorouracil (5-FU) for triple-negative breast cancer (TNBC) treatment. The PCG hydrogel was fabricated by blending synthesized [poly ( N -isopropyl acrylamide-co-itaconic acid), pNIAAm-co-IA, PNI] with CS in the presence of GP as a crosslinking agent. The interaction between PCG hydrogel compositions was characterized by Fourier transforms infrared, NMR spectroscopy, and scanning electron microscopy. The PCG hydrogel presented an interconnected and porous structure with similar pore size, rapid swelling/deswelling rate in response to both temperature and pH change, and biocompatibility, upon which it was proposed as a great drug carrier. 5-FU had a dual thermo- and pH-responsive controlled release behavior from the PCG hydrogel and displayed an accelerated release rate in an acidic pH environment than in a neutral pH condition. The application of 5-FU-loaded PCG hydrogel exhibited a more promoted anticancer activity than 5-FU against the growth of TNBC cells both in vitro and in vivo . The outcomes suggested that the PCG hydrogel could be an excellent platform for local drug-delivery systems in the clinical therapy of TNBC.