Characterization of Chitosan-Hybridized Diatomite as Potential Delivery Systems of Oxaliplatin and 5-Fluorouracil Drugs: Equilibrium and Release Kinetics.

Abstract

The current work involves the modification of diatomite's biosiliceous frustules employing chitosan polymer chains (CS/Di) to serve as low-cost, biocompatible, multifunctional, and enhanced pharmaceutical delivery systems for 5-fluorouracil (5-Fu) together with oxaliplatin (OXPL). The CS/Di carrier displayed strong loading characteristics, notably at saturation (249.17 mg/g (OXPL) and 267.6 mg/g (5-Fu)), demonstrating a substantial 5-Fu affinity. The loading of the two types of medications onto CS/Di was conducted based on the kinetic behaviors of the conventional pseudo-first-order theory (R2 > 0.90). However, while the loading of OXPL follows the isotherm assumptions of the classic Langmuir model (R2 = 0.99), the loading of 5-Fu displays Fruendlich isotherm properties. Therefore, the 5-Fu loading displayed physical, heterogeneous, and multilayer loading properties, whereas the loading of OXPL occurred in homogeneous and monolayer form. The densities of occupied active sites of CS/Di were 37.19 and 32.8 mg/g for the sequestrations of OXPL and 5-Fu, respectively. Furthermore, by means of multimolecular processes, each loading site of CS/Di can bind up to 8 molecules of OXPL and 9 molecules of 5-Fu in a vertical orientation. This observation explains the higher loading capacities of 5-Fu in comparison to OXPL. The loading energies, which exhibit values <40 kJ/mol, provide confirmation of the dominant and significant consequences of physical processes as the regulating mechanisms. The release patterns of OXPL and 5-Fu demonstrate prolonged features over a duration of up to 120 h. The release kinetic simulation and diffusion exponents which are more than 0.45 provide evidence of the release of OXP and 5-Fu via non-Fickian transportation characteristics and the erosion/diffusion mechanism. The CS/Di carrier exhibited a substantial enhancement in the cytotoxicity of OXPL and 5-Fu against HCT-116 carcinoma cell lines, resulting in a reduction in cell viability by 4.61 and 2.26% respectively.