Studies on polyethylene glycol crosslinked chitosan nanoparticles for co-delivery of docetaxel and 5-fluorouracil with synergistic effect against cancer

Targeting critical pathways of cancer cells using combination drugs is gaining significant importance as drug resistance is lowered and drug efficacy is improved even at low concentrations. Docetaxel and 5-fluorouracil are chemotherapeutic drugs prescribed for patients with solid tumours. While coated polymeric nanoparticles can combat drug resistance by sequential release of drugs, this paper proposes to encapsulate docetaxel and 5-fluorouracil in chitosan nanoparticles. To further improve the solubility of chitosan nanoparticles, they are crosslinked with polyethylene glycol using formaldehyde as crosslinker. Various techniques were used to characterize the nanoparticles. HR-SEM images indicated the formation of nanoparticles, drug loading into the chitosan nanoparticles and crosslinking of polyethylene glycol to chitosan nanoparticles. The experimental strategies were designed to evaluate the synergistic combination of the drugs in nanoparticles against AGS cell lines. It was found that the drugs loaded in chitosan nanoparticles synergistically inhibited the cell viability of AGS cells with a combination effect at 0.414. The combined effect of the drugs was even more effective, with value at 0.23 in the case of polyethylene glycol crosslinked-drug-loaded chitosan nanoparticles. The DPPH scavenging activity of drugs encapsulated in polyethylene glycol crosslinked chitosan nanoparticles was more effective at 57.39% compared to drug-alone counter parts. To further confirm the synergistic efficacy of the drugs loaded in nanoparticles in inducing apoptosis, changes were observed using acridine orange /ethidium bromide staining. Results indicated that combination effect of drugs in nanoparticles was much higher in AGS cells when compared to drug-alone incubated groups.

Graphical abstract

CsnNps@Dtl@Flul@Peg inhibits cell proliferation by disrupting microtubule disorganization and influencing RNA and DNA damage through sustained release of the drugs from the matrix