Insight into the integration effect of chitosan and β-cyclodextrin on the properties of zinc-phosphate/hydroxyapatite hybrid as delivery structures for 5-fluorouracil: loading and release profiles

May N Bin Jumah; Sarah I Al Othman; Awatif Abdulaziz Alomari; Ahmed A Allam; Stefano Bellucci; Mostafa R Abukhadra

doi:10.3389/fchem.2024.1456057

Insight into the integration effect of chitosan and β-cyclodextrin on the properties of zinc-phosphate/hydroxyapatite hybrid as delivery structures for 5-fluorouracil: loading and release profiles

Front Chem. 2024 Sep 11:12:1456057. doi: 10.3389/fchem.2024.1456057. eCollection 2024.

Authors

May N Bin Jumah¹, Sarah I Al Othman¹, Awatif Abdulaziz Alomari¹, Ahmed A Allam^{2

3}, Stefano Bellucci⁴, Mostafa R Abukhadra^{5

6}

Affiliations

¹ Biology Department, College of Science, Princess Nourah bint Abdulrahman University, Riyadh, Saudi Arabia.
² Zoology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
³ Department of Biology, College of Science, Imam Mohammad Ibn Saud Islamic University (IMSIU), Riyadh, Saudi Arabia.
⁴ INFN-Laboratori Nazionali di Frascati, Frascati, Italy.
⁵ Geology Department, Faculty of Science, Beni-Suef University, Beni-Suef, Egypt.
⁶ Materials Technologies and their Applications Lab, Geology Department, Faculty of Science, Beni-Suef University, Beni-Suef City, Egypt.

Abstract

Zinc-phosphate/hydroxyapatite hybrid form (ZP/HP) in core-shell nanostructure was developed and functionalized with both chitosan (CS@ZP/HP) and β-cyclodextrin (CD@ZP/HP) as bio-composite of enhanced physicochemical and biological properties. These structures were assessed as potential deliveries of 5-fluorouracil, exhibiting enhanced loading, release, and anti-cancer behaviors. The functionalization strongly prompted the loading effectiveness to be 301.3 mg/g (CS@ZP/HP) and 342.8 mg/g (CD@ZP/HP) instead of 238.9 mg/g for ZP/HP. The loading activities were assessed based on the hypotheses of traditional kinetic and isotherm models, alongside the computational variables of the monolayer model with a single energetic site as an advanced isotherm model. The functionalized versions exhibit much greater loading efficacy compared to ZP/HP as a result of the increment in the density of the existing loading sites [Nm_(5-Fu) = 78.85 mg/g (ZP/HP), 93.87 mg/g (CS@ZP/HP), and 117.8 mg/g (CD@ZP/HP)]. Furthermore, the loading energies of approximately 40 kJ/mol, together with the loading potential of each receptor (n > 1) and Gaussian energies of approximately 8 kJ/mol, indicate the physical entrapment of 5-Fu molecules according to a vertical orientation. The materials mentioned verify long-term and continuous release characteristics. Following the modification processes, this behavior became faster as both CS@ZP/HP and CD@ZP/HP displayed complete release within 120 h at pH 1.2. The kinetic studies and diffusing exponent (>0.45) indicate that release characteristics are controlled by both diffusion and erosion processes. These carriers also markedly increase the cytotoxicity of 5-Fu against HCT-116 colorectal cancer cell lines: 5-Fu-ZP/HP (3.2% cell viability), 5-Fu-CS@ZP/HP (1.12% cell viability), and 5-Fu-CD@ZP/HP (0.63% cell viability).

Keywords: 5-fluorouracil; anticancer; biopolymers; composites; hydroxyapatite; loading.

Grants and funding

The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This work was funded by the Deanship of Scientific Research at Princess Nourah bint Abdulrahman University, through the Research Groups Program Grant no. (RGP-1444-0035) (2).