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

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 nano composite 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.

Automated summary

Chitosan was functionalized and utilized as smart pH-responsive drug delivery systems for the anticancer drug cyclophosphamide. Different synthesized materials showed varied drug release rates under different pH conditions, with CS-AC-U-CP being identified as the most desirable DDS.