Development of photo and pH dual crosslinked coumarin-containing chitosan nanoparticles for controlled drug release

• Published in: Carbohydrate polymers 2018-12, Vol.201, p.236-245
• Main Authors: Rahimi, Shahnaz, Khoee, Sepideh, Ghandi, Mehdi
• Format: Article
• Language: English
• Subjects: Chitosan; Chitosan - chemistry; Chitosan - pharmacology; Coumarin; Coumarins - chemistry; Coumarins - pharmacology; Cross-Linking Reagents - chemistry; Delayed-Action Preparations - chemistry; Delayed-Action Preparations - pharmacology; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug delivery system; HeLa Cells; Humans; Hydrogen-Ion Concentration; Nanoparticles; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Photo- and pH-responsive; Photochemical Processes
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2018.08.074

[Display omitted] •Photo- and pH-responsive iminocoumarin-chitosan nanoparticles were prepared.•These nanoparticles were photo-crosslinked via [2 + 2] cycloaddition reaction.•Under UV-irradiation, microcapsules were formed via [2 + 2] inter-particle reactions.•Microparticles shell were cleaved and fragmented by increasing the exposure time.•Drug-loaded chitosan–coumarin nanoparticles showed anticancer properties. A new strategy has been developed to the fabrication of chitosan nanoparticles as anticancer drug nanocarriers with ultraviolet-responsive coumarin derivatives and pH-responsive imine groups. For this purpose 8-formyl-7-hydroxy-4-methylcoumarin (8-FHMC) was initially synthesized as novel and dual crosslinking agent in order to produce coumarin-containing chitosan nanoparticles via oil-in-water nanoemulsion system. The structure of the resultant compounds and nanoparticles were confirmed by means of 1H NMR, FT-IR, UV–vis spectroscopy and XRD. The morphology and size distribution of the coumarin-containing chitosan nanoparticles was also characterized using SEM, AFM and DLS. The drug-loaded coumarin-containing chitosan nanoparticles were stable at physiological conditions, and can also be disassociated by the cleavage of imine linkages in the crosslinking segments under acidic condition. Compared to non-photo-crosslinked chitosan nanoparticles, photo-crosslinked chitosan nanoparticles displayed controllable and slower release. Thus, we have showed that chitosan nanoparticles crosslinked by coumarin with photo- and pH-responsive properties is a promising and novel drug carrier for designing intelligent drug delivery systems.