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

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 (R 2 = 0.99) and kinetic assumptions of pseudo-first order kinetic (R 2 > 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).

Different Drug Mobilities in Hydrophobic Cavities of Host–Guest Complexes between β-Cyclodextrin and 5-Fluorouracil at Different Stoichiometries: A Molecular Dynamics Study in Water

“…1 mg/mL) [ 58 ]. Appropriate carriers or substrates can enhance its bioavailability and mitigate the development of serious side effects [ 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Molecular simulations of the adsorption process of 5-FU on graphene oxide nanosheets as a drug delivery vehicle [ 72 ], MD simulations related to hydrophilic pores in phospholipid bilayers and Fe 3 O 4 nanoparticles loaded with 5-FU [ 73 ], and investigations into the adsorption of 5-FU on gold clusters [ 74 , 75 ] have attracted attention.…”