PH-responsive prodrug containing Zr-based MOF and aldehyde-based drug; anionic hydrogel coating as a smart delivery system

Abstract

In this work, a metal organic framework (MOF)-based prodrug was fabricated via Schiff base reaction between UiO-66-NH2 and 3,4-dihydroxybenzaldehyde (DHBD) drug to form DHBD@MOF prodrug containing pH-sensitive C=N bonding. Moreover, a dual pH-responsive drug delivery platform containing (5-Fluorouracil) 5-FU drug and DHBD@MOF prodrug entrapped by carboxymethyl cellulose (CMC) and alginate (Alg.) hydrogel (DHBD@MOF/5-FU@CMC/Ca2+/Alg.) was developed. Then, the characteristics of prodrug and delivery system were analyzed using PXRD, FT-IR, FE-SEM, TEM,and BET techniques. The in vitro and cumulative release results revealed that the fabricated platform was protected successfully by hydrogel from burst release in acidic condition of stomach and small intestine so that 1.31% release of DHBD from DHBD@MOF/5-FU@CMC/Ca2+/Alg was recorded after 2.5 h at pH 1.2, while DHDB release from DHBD@MOF prodrug (without hydrogel) was about 90% after 2.5 h at pH 1.2. The synthesized hydrogel could control the release of drug in a smart controlled manner at specific sites so that after hydrogel swelling at intestine and colorectum at pH around 6.5–7.4 and prodrug release, pH-sensitive C=N bonding of DHBD@MOF is cleaved at acidic colorectum cancer sites, and the inactive prodrug is efficiently activated. The hydrogel could successfully control the release of DHBD and 5-FU in SGF (simulated gastric fluid, at different pHs) from DHBD@MOF/5-FU@hydrogel at different pHs of 1.2, 4.5, 7.4 and 6.5, so that the gradual release of DHBD from DDDS in intestine (pH 7.4) and colorectum (pH 6.5) after 8.5 h and 24 was 10.60 and 41.68%, respectively, where 89.40 and 58.32% of inactive DHDB@MOF prodrug after 8.5 and 24 h could access to the acidic tumors (cancer sites). The findings of this research can be applied for medical science and pharmaceutics after completing the in vivo experiments.