Design and Characterization of a Bioinspired PAMAM@Poly(Caffeic Acid) Magnetite Nanocarrier for Curcumin Delivery

Efficient intracellular drug delivery requires well-designed nanocarriers capable of stabilizing and releasing bioactive compounds in a controlled manner. Here, we introduce a bioinspired nanohybrid system that integrates generation 4.0 poly-(amidoamine) (PAMAM) dendrimers with poly-(caffeic acid)-coated magnetite nanoparticles (PCA@Fe₃O₄) to achieve efficient, long-lasting delivery of curcumin. Encapsulation within the PAMAM-PCA@Fe₃O₄ framework markedly improves curcumin stability and supports controlled release, with a total loading of approximately 190 μg of curcumin per sample as quantified by UV-Vis spectroscopy at 429 nm. AFM measurements showed progressive size increases from ∼26 nm for bare Fe₃O₄ to ∼43 nm for PCA@Fe₃O₄ and ∼66 nm for PAMAM-PCA@Fe₃O₄, while TEM analyses confirmed the spherical morphology of the nanoparticles. Release studies in PBS (pH 7.4, 37 °C) demonstrated a gradual and sustained release profile, with ∼33% of the encapsulated curcumin (∼64 μg) released over 24 h. In vitro cytotoxicity assays in MRC-5 fibroblasts indicated that PAMAM-PCA@Fe₃O₄ was biocompatible, whereas curcumin-loaded nanohybrids produced dose-dependent cytotoxicity consistent with curcumin's known biological activity.