Curcumin-Loaded Poly(xylitol sebacate) Nanoparticles Reduce Viability and Alter Morphology in Colorectal Cancer Cell Lines

Abstract

Background/Objectives: Poly(xylitol sebacate) (PXS) is a biodegradable, biocompatible hyperbranched polyester capable of self-assembling into nanoparticles for hydrophobic drug delivery. Building on our prior physicochemical characterization of PXS nanoparticles, this study evaluated whether curcumin-loaded PXS nanoparticles (LNP) can deliver curcumin to colorectal cancer (CRC) cells and enhance its anticancer activity relative to free curcumin. Methods: Unloaded (UNP) and curcumin-loaded PXS nanoparticles were fabricated by nanoprecipitation and characterized by dynamic light scattering (DLS) and scanning electron microscopy (SEM). Four CRC cell lines (HCT116, HT29, SW480, SW620) were treated with free curcumin, UNP, or LNP at an equivalent curcumin concentration of 20 μg/mL for 48 h; viability was measured by CellTiter-Blue® assay, and cell morphology and curcumin cellular association were assessed by phase-contrast and fluorescence microscopy. Results: Nanoparticles fell within the target 100–200 nm range (LNP: 171.04 nm; UNP: 212.40 nm at 24 h) and remained colloidally stable for 48 h (159–203 nm). SEM confirmed spherical morphology for both formulations, and UNP were not cytotoxic at 20 μg/mL. LNP produced substantially greater viability reduction than free curcumin across all lines: SW480 and SW620 decreased to ~30% viability (~70% reduction), HT29 to ~60% (~40% reduction, despite minimal response to free curcumin), and HCT116, the most resistant line, to ~70% (~30% reduction). Fluorescence imaging suggested closer cellular association of LNP-delivered curcumin, although the signal was modest and not quantified. Conclusions: PXS nanoparticles are an effective, biodegradable carrier that enhances the cellular delivery and anticancer activity of curcumin in CRC cells, supporting further development of this hyperbranched polyester platform for cancer drug delivery.