Development of a photoresponsive chitosan conjugated prodrug nanocarrier for controlled delivery of antitumor drug 5-fluorouracil

Controlled drug delivery offers improved therapeutic efficacy of the drugs while minimizing side effects. Biocompatible polymers and nanomaterials have emerged as effective carriers for the controlled delivery of drugs. We have synthesized a prodrug of 5-fluorouracil (5FU) covalently conjugated to low molecular weight chitosan (LMWC) via a photocleavable linker. The conjugate was designed to be cleaved under 365 nm UV-A radiations, which is regarded as relatively safe for the cells and release 5FU in a dose-dependent manner. The conjugate showed enhanced water solubility compared to LMWC and forms hydrogel and DMSO gel. The conjugate polymer was also fabricated into nanoparticles by ionic gelation technique. The size of the nanoparticles was found to be in the range 70-90 nm, thus should have the ability to penetrate into living cells. In vitro release study of 5FU from the conjugate showed controlled release of the antitumor drug over time. The synthesized nanoparticles and the gel, therefore, could be a good model for controlled release of antitumor drugs. (C) 2018 Elsevier B.V. All rights reserved.