Insights into the Effect of Chitosan and β-Cyclodextrin Hybridization of Zeolite-A on Its Physicochemical and Cytotoxic Properties as a Bio-Carrier for 5-Fluorouracil: Equilibrium and Release Kinetics Studies

Molecules. 2023 Jul 15;28(14):5427. doi: 10.3390/molecules28145427.

Abstract

Synthetic zeolite-A (ZA) was hybridized with two different biopolymers (chitosan and β-cyclodextrin) producing biocompatible chitosan/zeolite-A (CS/ZA) and β-cyclodextrin/zeolite-A (CD/ZA) biocomposites. The synthetic composites were assessed as bio-carriers of the 5-fluorouracil drug (5-Fu) with enhanced properties, highlighting the impact of the polymer type. The hybridization by the two biopolymers resulted in notable increases in the 5-Fu loading capacities, to 218.2 mg/g (CS/ZA) and 291.3 mg/g (CD/ZA), as compared to ZA (134.2 mg/g). The loading behaviors using ZA as well as CS/ZA and CD/ZA were illustrated based on the classic kinetics properties of pseudo-first-order kinetics (R2 > 0.95) and the traditional Langmuir isotherm (R2 = 0.99). CD/ZA shows a significantly higher active site density (102.7 mg/g) in comparison to CS/ZA (64 mg/g) and ZA (35.8 mg/g). The number of loaded 5-Fu per site of ZA, CS/ZA, and CD/ZA (>1) validates the vertical ordering of the loaded drug ions by multi-molecular processes. These processes are mainly physical mechanisms based on the determined Gaussian energy (<8 kJ/mol) and loading energy (<40 kJ/mol). Both the CS/ZA and CD/ZA 5-Fu release activities display continuous and controlled profiles up to 80 h, with CD/ZA exhibiting much faster release. According to the release kinetics studies, the release processes contain non-Fickian transport release properties, suggesting cooperative diffusion and erosion release mechanisms. The cytotoxicity of 5-Fu is also significantly enhanced by these carriers: 5-Fu/ZA (11.72% cell viability), 5-Fu/CS/ZA (5.43% cell viability), and 5-Fu/CD/ZA (1.83% cell viability).

Keywords: 5-fluorouracil; biopolymers; composites; cytotoxicity; loading; zeolite-A.

MeSH terms

  • Antineoplastic Agents*
  • Chitosan* / chemistry
  • Drug Carriers / chemistry
  • Fluorouracil / chemistry
  • Fluorouracil / pharmacology
  • Kinetics
  • Zeolites*
  • beta-Cyclodextrins* / chemistry

Substances

  • Fluorouracil
  • Chitosan
  • Zeolites
  • Antineoplastic Agents
  • Drug Carriers
  • beta-Cyclodextrins

Grants and funding

This work was funded by the Deanship of Scientific Research at the Princess Nourah Bint Abdulrahman University, through the Research Groups Program (grant no. RGP-1443-0050).