5-Fluorouracil monodispersed chitosan microspheres: Microfluidic chip fabrication with crosslinking, characterization, drug release and anticancer activity

Abstract

Different size and morphology monodispersed chitosan (CS) microspheres loaded with the anticancer drug of 5-fluorouracil (5-Fu) were prepared by the microfluidic method assisted by a crosslinking unit with crosslinkers of tripolyphosphate (TPP) and glutaraldehyde (GTA). The sizes, morphologies, drug loading, encapsulation efficiency, drug release and cytotoxicity of 5-Fu loaded CS microspheres were characterized and determined. Results indicated that the CS microspheres were uniform in size distributions. They possessed excellent encapsulation efficiency and drug loading. The TPP-crosslinked CS microspheres had rough surfaces and exhibited faster drug release, whereas the CS microspheres crosslinked with GTA had smooth surfaces and showed slower drug release. Furthermore, 5-Fu-loaded CS microspheres exhibited sustained drug release which well fitted the first-order kinetics model and were pH-responsive in that the drug cumulative release was greater at acidic environments than at neutral conditions. Finally, 5-Fu loaded CS microspheres provided sufficient cytotoxicity and were satisfactory in the cancer cell inhibition.

Keywords: 3-(4,5-Dimethylthi-ozol-2-yl) -2,5-diphenyl tetrazolium bromide (MTT, Pubchem CID: 64965); 5-Fluorouracil; 5-fluorouracil (Pubchem CID: 3385); Acetic acid (Pubchem CID:176); Anticancer activity; Chitosan (Pubchem CID: 21896651); Crosslinking; Drug release; Ethanol (Pubchem CID: 702); Glutaraldehyde (GTA, Pubchem CID: 3485); Isopropanol (Pubchem CID: 3776); Microfluidic chip; Monodispersed chitosan microspheres; Sodium dihydngen phosphate anhydrous (Pubchem CID: 23672064); Sodium phosphate dibasic (Pubchem CID: 24203); Tripolyphosphate (TPP, Pubchem CID: 24455).