Controlled release, Ionic gelation, Cellular internalization, Biocompatibility, Therapeutic efficacy, Engineering (General). Civil engineering (General), TA1-2040

In this study, we developed a novel drug delivery system based on polysaccharides extracted from Atractylodes macrocephala rhizomes. Using ultrasonic-assisted enzymatic extraction, we successfully isolated heteropolysaccharides with a predominant glucose composition (67.3 %) and molecular weight of 145 kDa. The ionic gelation method with STMP yielded uniform spherical nanoparticles exhibiting a negative surface charge of −32.4 mV and monomodal size distribution around 168 nm. The nanoparticles demonstrated remarkable stability over 30 days at 4°C with less than 5 % size variation. Using curcumin as a model drug, the system achieved 78.5 % encapsulation efficiency and displayed pH-sensitive release behavior, with accelerated release at pH 5.0 (89.2 %) compared to pH 7.4 (76.4 %) over 72 hours. The nanoformulation enhanced cellular uptake through clathrin-mediated endocytosis, with 78.3 % internalization after 6 hours. Cytotoxicity studies revealed minimal carrier toxicity (IC50 > 2000 μg/mL) while improving curcumin's therapeutic efficacy by reducing IC50 from 45.7 to 22.3 μg/mL in MDA-MB-231 cells. The degree of sulfation (DS = 1.2) was identified as a critical parameter affecting cellular internalization and therapeutic performance.