Smart Hybrid Nanocontainers: Layered Double Hydroxide Nanoparticles Modified with Thermoresponsive Polymers

Layered double hydroxides (LDH), degradable class of clay, have garnered increasing attention as promising drug delivery systems due to their unique brucite-like structure that enables efficient anion exchange. This research addresses the development of smart hybrid nanocontainers (SHNs) for drug delivery by synthesizing LDH-based nanocarriers conjugated with the thermoresponsive polymer, poly(2-(2-methoxyethoxy)ethyl methacrylate) (P(MEO 2 MA)). The synthetic strategy involves the synthesis of LDH nanoparticles intercalated with methotrexate (LDH-MTX), their subsequent functionalization with terminal vinyl groups, and finally a free-radical polymerization assisted by ultrasound to form thermoresponsive nanohybrids. The present work focuses on optimizing the synthesis and chemical functionalization of the SHNs and establishing a proof of concept for drug release using MTX as a model compound. Specifically, we investigated the influence of the functionalized nanoparticles (LDH-MTX@MEMO) on the colloidal stability and thermoresponsive behavior of the resulting SHNs. The results demonstrate that incorporation of the smart polymer markedly improves colloidal stability, dispersibility, and controlled MTX release, particularly when the drug is loaded prior to polymerization (LDH-MTX/MEO 2 MA). Overall, these findings confirm that the developed SHNs are stable, thermoresponsive, and efficient nanocontainers.