Mitochondria targeted chitosan alginate nanoparticles for rooibos (Aspalathus linearis) delivery

Developments in the field of nanomedicine demonstrate that antioxidant-loaded nanoparticles (NPs) may improve targeted drug delivery. Aspalathus linearis (rooibos, RB) is a natural polyphenol-rich plant extract that exhibits anti-inflammatory and antimutagenic effects. However, few studies have developed RB-enriched NPs for targeted intracellular delivery. This study aimed to synthesize and characterize novel RB-loaded chitosan-alginate nanoparticles (CS-ALG NPs) that are specifically targeted to mitochondria. NPs were characterized using FTIR and 1 H NMR spectroscopy, confirming functionalization with the mitochondria-targeting ligand, triphenylphosphonium (TPP). Confocal imaging demonstrated cellular uptake of RB-TPP-CS-ALG NPs in MCF-7 cells, while quantitative analysis supported their mitochondrial co-localization. Physicochemical characterization revealed a spherical morphology, with the optimized formulation exhibiting a particle size of 362.9 nm, uniform dispersion (0.177 ± 0.08), and high colloidal stability (32.5 ± 2.3 mV). RB-TPP-CS-ALG NPs demonstrated diffusion-controlled RB release with significantly higher release under acidic conditions. Particles remained stable during storage for 30 days at 4 °C. RB-TPP-CS-ALG NPs exhibited a dose-dependent cytotoxic response against MCF-7 cells compared to the untreated control. The mitochondria-targeting capability, sustained RB release, pH-responsive behavior, and cytotoxic response in MCF-7 cells support their further investigation as a mitochondria-targeted intracellular drug delivery system.