The objective of this study is to develop a nanostructured parenteral delivery system, laden with curcumin (CUR), for the therapeutic intervention of sepsis and associated pathologies. Nanoemulsions were fabricated using sonication and speed homogenization. Size and zeta potential were evaluated by dynamic light scattering and transmission electron microscopy analysis. Pharmacodynamic and pharmacokinetic studies were performed on a rat model of lipopolysaccharide (LPS)-induced sepsis. The drug content of optimized nanoemulsion (F5) formulation (particle size 246 ± 08 nm, polydispersity index (PDI) of 0.120, zeta potential of -41.1 ± 1.2 mV) was found to be 1.25 mg/ml. In vitro release studies demonstrated that F5 was able to sustain the release of CUR for up to 24 h. Minimal hemolysis and cellular toxicity demonstrated its suitability for intravenous administration. Significant reduction of inflammatory mediator levels was mediated through enhanced uptake by in RAW 264.7 and THP-1 in absence/presence of LPS. Nanoemulsion resulted in an improvement of plasma concentration (AUCF5/AUC CUR = 8.80) and tissue distribution of CUR in rats leading to a reduction in LPS-induced lung and liver injury due to less neutrophil migration, reduced TNF-α levels and oxidative stress (demonstrated by levels of lipid peroxides as well as carbonylated proteins) as confirmed by histopathological studies. The findings suggest that the therapeutic performance (i.e., reduction in oxidative damage in tissues) of CUR can be enhanced by employing tocol acetate nanoemulsions (via improving pharmacokinetics and tissue distribution) as a platform for drug delivery in sepsis-induced organ injury.

The global rise in diabetes mellitus has been paralleled by an increase in associated complications, notably impaired Wound Healing. Non-healing diabetic wounds are driven by multifactorial pathogenesis involving hyperglycemia, immune dysfunction, impaired angiogenesis, bacterial infections, and increased oxidative stress. Traditionally, a variety of plant-derived extracts and phytochemicals such as quercetin, curcumin, and paeoniflorin have been employed in the treatment of diabetic wounds worldwide. These agents exert their therapeutic effects primarily through antioxidant, antibacterial, anti-inflammatory, and pro-angiogenic mechanisms and properties, typically with minimal side effects. Recent advancements have highlighted the potential of integrating phytoconstituents with metal nanoparticles to enhance Wound Healing efficacy. Nanoformulations improve targeted phytochemical delivery and offer synergistic benefits due to intrinsic antimicrobial and antioxidant properties, enhanced antioxidant activity, and high biocompatibility. Similarly, polymeric nanocarrier-based delivery systems have emerged as a promising strategy to address the limitations of conventional wound treatments, promoting faster and more efficient healing in diabetic patients. This review comprehensively discusses the pathophysiology and clinical challenges associated with diabetic Wound Healing, explores the therapeutic potential of key phytochemicals, and presents the current progress in nanoparticle-based delivery systems (metallic and polymeric) for diabetic wound management. Additionally, it provides an update on recent patents and clinical trials involving phytoconstituents and their formulations for the treatment of diabetic wounds.