Curcumin-Fullerene Nanoantioxidant Treats Ulcerative Colitis through Antioxidant and Anti-Inflammatory Mechanisms

Active compounds derived from traditional Chinese medicine have attracted considerable interest as potential strategies for alleviating inflammation. However, their clinical translation is often impeded by limitations, including poor bioavailability and unsatisfactory therapeutic efficacy. To overcome these challenges, a novel fullerene-based nanoantioxidant was developed to enable oral administration and achieve site-specific targeting of inflammatory regions, thereby improving the therapeutic performance of curcumin (CUR) in ulcerative colitis. HA-C60 was synthesized through amidation between amino groups on aminated fullerene and carboxyl groups on hyaluronic acid, yielding a carrier with intrinsic anti-inflammatory properties. <i>In vitro</i> studies demonstrated that the carrier possessed free radical scavenging activity. After encapsulation within HA-C60, the resulting CUR nanoparticle formulation (CUR@HA-C60) exhibited both targeted and synergistic anti-inflammatory effects. This carrier markedly enhanced CUR stability in the upper gastrointestinal tract and facilitated site-specific drug accumulation at inflamed colonic sites. Anti-inflammatory efficacy was confirmed by reduced levels of nitric oxide, tumor necrosis factor-α, interleukin-1β, myeloperoxidase, and malondialdehyde, alongside increased expression of interleukin-10, superoxide dismutase, and glutathione, thereby mitigating inflammatory responses and oxidative stress (OS). Furthermore, CUR@HA-C60 demonstrated favorable biosafety profiles in murine models and significantly improved CUR bioavailability by suppressing inflammation, reducing OS-related damage, and restoring intestinal epithelial integrity. These findings indicate that CUR@HA-C60 represents a promising oral therapeutic strategy for the treatment of inflammatory diseases.