Alginate/magnetic hydroxyapatite bio-nanocomposite hydrogel bead as a pH-responsive oral drug carrier for potential colon cancer therapy
Rauf Foroutan, Ali Mohammadzadeh, Siamak Javanbakht, Réza Mohammadi, Marjan Ghorbani
Abstract
In this study, a biocompatible pH-sensitive magnetic nanocomposite hydrogel bead was developed as a potential oral drug carrier. Fe 3 O 4 nanoparticles (NPs) were in situ synthesized in the presence of hydroxyapatite (HAp) NPs as substrate and the HAp-Fe 3 O 4 nanohybrid was then incorporated into the pH-sensitive sodium alginate (SA) biopolymer. Ultimately, 5-Fluorouracil (5-FU) as an anticancer drug was successfully loaded in the SA/HAp-Fe 3 O 4 . The SA/HAp-Fe 3 O 4 hydrogel bead shows minimal swelling in acidic environments (pH 1.2) and significant swelling in alkaline environments (pH 7.4). Additionally, drug release studies demonstrated that this drug delivery system was able to retain the drug in the acidic stomach environment and release it in the higher pH of the intestine. Kinetic analysis of the release profiles indicated that the release rate was primarily controlled by Fickian diffusion, which is a process governed by diffusion without interaction between the polymer matrix and the drug. The cytotoxicity results investigated by the MTT assay indicated good cytocompatibility for the SA/HAp/Fe 3 O 4 magnetic nanocomposite hydrogel bead, with cell viability exceeding 85 % in 4 to 48 μg/mL ( P < 0.05); however, 5-FU-loaded SA/HAp-Fe 3 O 4 showed noticeable toxicity against HT-29 human colon cancer cells. Based on the pH-sensitivity, controlled release, and cytotoxicity data, the prepared magnetic nanocomposite hydrogel bead could serve as a targeted oral drug delivery system for colon cancer therapy. • SA/HAp/Fe 3 O 4 magnetic bio-nanocomposite hydrogel bead was successfully synthesized. • SA/HAp/Fe 3 O 4 magnetic bio-nanocomposite hydrogel bead has a desired pH-responsive 5-FU delivery property. • 5-FU-loaded SA/HAp/Fe 3 O 4 magnetic bio-nanocomposite hydrogel bead showed notable cytotoxicity toward HT-29 cells. • The 5-FU release rate at pH 1.2 was significantly higher than pH 7.4.