MOF-based prodrug entrapped in carboxymethyl cellulose and alginate hydrogel: A drug delivery platform

Abstract

In this study, a metal-organic framework (MOF)-based prodrug was synthesized through a Schiff base reaction between UiO-66-NH₂ and 3,4-dihydroxybenzaldehyde (DHBD) drug, resulting in the formation of DHBD@MOF prodrug containing a pH-sensitive C = N bond. Additionally, a dual pH-responsive drug delivery platform was developed, which encapsulated both 5-Fluorouracil (5-FU) drug and DHBD@MOF prodrug within a hydrogel composed of carboxymethyl cellulose (CMC) and alginate (Alg.). The characteristics were analyzed using PXRD, FT-IR, FE-SEM, TEM, and BET. The release studies demonstrated that the hydrogel effectively protected the platform from burst release in the acidic conditions of the stomach and small intestine. Only 1.31% release of DHBD from DHBD@MOF/5-FU@hydrogel was observed after 2.5 h at pH 1.2, compared to near 90% release from DHBD@MOF prodrug under the same conditions. Upon swelling of the hydrogel in the intestine and colorectum at pH around 6.5–7.4, pH-sensitive C = N bonding of DHBD@MOF was cleaved at acidic colorectal cancer sites, activating the inactive prodrug. Furthermore, the hydrogel facilitated controlled release of DHBD and 5-FU in simulated gastric fluid (SGF) at different pH levels (1.2, 4.5, 7.4, and 6.5). The gradual release of DHBD from hydrogel in the intestine (pH 7.4, 8.5 h) and colorectum (pH 6.5, 24 h) was 10.60% and 41.68%, respectively. This allowed for significant accumulation of the inactive DHBD@MOF prodrug at acidic tumor sites, with 89.40% and 58.32% accessing the tumors after 8.5 h and 24 h, respectively. The findings of this research hold promise for applications in medical science and pharmaceutics after in vivo experiments.