Synthesis and Characterization of Mg-Hydroxyapatite and Its β-Cyclodextrin Composite as Enhanced Bio-Carrier of 5-Fluorouracil Drug; Equilibrium and Release Kinetics

Mostafa R. Abukhadra, Alaa T. Okasha, Sarah I. Al Othman, Haifa E. Alfassam, Noof A. Alenazi, Ali A. AlHammadi, Ahmed A. Allam

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    Abstract

    An advanced form of magnesium-doped hydroxyapatite (Mg·HAP) was integrated in composite with β-cyclodextrin producing a safe biocomposite (β-CD/HAP) as an enhanced delivery structure of traditional 5-fluorouracil (5-FU) chemotherapy during the treatment stages of colorectal cancer cells. The qualifications of β-CD/HAP as a carrier for 5-FU were followed based on the loading, release, and cytotoxicity as compared to Mg·HAP. β-CD/HAP composite exhibits notably higher 5-FU encapsulation capacity (272.3 mg/g) than Mg·HAP phase (164.9 mg/g). The 5-FU encapsulation processes into β-CD/HAP display the isotherm behavior of the Freundlich model (R2 = 0.99) and kinetic assumptions of pseudo-first order kinetic (R2 > 0.95). The steric studies reflect a strong increment in the quantities of the free sites after the β-CD integration steps (Nm = 61.2 mg/g) as compared to pure Mg·HAP (Nm = 42.4 mg/g). Also, the capacity of each site was enhanced to be loaded by 5 of 5-FU molecules (n = 4.45) in a vertical orientation. The 5-FU encapsulation energy into β-CD/HAP (<40 kJ/mol) reflects physical encapsulation reactions involving van der Waals forces and hydrogen bonding. The 5-FU release profiles of β-CD/HAP exhibit slow and controlled properties for about 80 h either in gastric fluid (pH 1.2) or in intestinal fluid (pH 7.4). The release kinetics and diffusion exponent (>0.45) signify non-Fickian transport and complex erosion/diffusion release mechanism. The free β-CD/HAP particles display a considerable cytotoxic effect on the HCT-116 cancer cells (33.62% cell viability) and its 5-FU-loaded product shows a strong cytotoxic effect (2.91% cell viability).

    Original languageBritish English
    Pages (from-to)30247-30261
    Number of pages15
    JournalACS Omega
    Volume8
    Issue number33
    DOIs
    StatePublished - 22 Aug 2023

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