Experimental and computational insights into the design of pH-responsive sodium alginate-coated nanoparticles for targeted mesalazine delivery

Halloysite-alginate beads loaded with mesalazine or 5-amino salicylic acid (5-ASA), a model anti-inflammatory drug, were investigated for their ability to protect the drug from acidic degradation during gastrointestinal transit. X-ray fluorescence (XRF) analysis confirmed the composition of the halloysite nanotubes, while zeta potential analysis corroborated their colloidal stability. Fourier transform infrared (FT-IR) spectroscopy, ther mogravimetric analysis (TGA), and X-ray diffraction (XRD) investigations confirmed the effective production of the nanocomposite and provided insights into the interactions between its components and crystalline structure. The structure and homogeneous size distribution of the halloysite nanotubes (HNT) were examined using transmission electron microscopy (TEM). Additionally, scanning electron microscopy (SEM) images indicated a spherical shape and a relatively rough bead surface. Upon initial incubation in a simulated gastric medium (pH 1.2), the beads remained unchanged. In contrast, incubation in a simulated intestinal medium (pH 6.8) led to bead swelling, floating, and erosion. Furthermore, the formulation exhibited a smart, pH-sensitive release mechanism, achieving complete drug release over 750minutes, highlighting its potential for sustained and targeted drug delivery. Release data for 5-ASA were well-fitted to the Korsmeyer-Peppas and Higuchi models, indicating distinct mechanisms governing the release from the composite material. Density functional theory (DFT) analyses revealed specific interactions between 5-ASA and halloysite, characterized by strong hydrogen bonding and Lewis acid-base interactions with aluminol sites, alongside reduced van der Waals forces in the hydrophobic siloxane regions.