Smart pH-responsive drug release systems based on functionalized chitosan nanocomposite hydrogels

Abstract

Chitosan (CS) was functionalized by formaldehyde (FA), acetaldehyde (AC), formaldehyde-urea (FA-U) and acetaldehyde-urea (AC-U) and the synthesized materials were utilized as efficient smart pH-responsive drug delivery systems (DDSs) for the cyclophosphamide (CP) anticancer drug. For this purpose, polymeric nanocomposite hydrogels were fabricated using CS-FA, CS-AC, CS-FA-U and CS-AC-U, carbon quantum dots (CQDs) as the filler as well as glycerol and the poly(ethylene oxide) (PEO) as plasticizers. The highest swelling degrees were happened in the acidic solution (2150–4300%), medium amounts in neutral pH (620–1250%) and the smallest values were observed within the alkaline pH (260–435%). The release percentages in three acidic, PBS buffer and alkaline solutions varied in the range of 64.5–77.7, 49.7–61.2 and 37.7–46.8%, respectively, illustrating a pH-responsive drug delivery which was approved by the statistical ANOVA tests. The CP release was significantly boosted within about 2–5 h, burst release, whereas release of the drug was subsequently slowly increased in 24 h demonstrating a sustained drug release. The kinetics of the drug release was examined for all of the DDSs and it was revealed that the Korsmeyer-Peppas was the best model as it was well matched to the drug release kinetics. The CS-FA-U-CQDs-CP and CS-AC-U-CQDs-CP were introduced as suitable slow-release drug carriers. It was finally found that the CS-AC-U-CP was the most desirable DDS as it simultaneously displayed favorable controlled, pH-responsive and high amount of drug release which followed the US Pharmacopeia drug release in acidic solution.