The study aims to develop high drug-loaded (about 15% lipid matrix) curcumin solid lipid nanoparticles (CSLNs) for wound healing. CSLNs prepared by hot, high-pressure homogenization, without using organic solvents, were optimized using the Taguchi design followed by the central composite design. The optimized CSLNs exhibited a high assay/drug content (0.6% w/w), solubility (6 × 105 times), and EE (75%) with a particle size < 200 nm (PDI—0.143). The CSLNs were safe (in vitro and in vivo), photostable, autoclavable, stable up to one year at 30 °C and under refrigeration and exhibited a controlled release (zero-order; 5 days). XRD, FTIR, and DSC confirmed solubilization and entrapment of the curcumin within the SLNs. TEM and FESEM revealed a smooth and spherical shape. The CSLNs showed a significant antimicrobial effect (MIC of 64 µg/mL for planktonic cells; 512 µg/mL for biofilm formation; and 2 mg/mL for mature biofilm) against Staphylococcus aureus 9144, while free curcumin dispersion did not exhibit any effect. This is the first report on the disruption of mature biofilms by curcumin solid lipid nanoparticles (CSLNs). The cell proliferation potential of CSLNs was also evaluated in vitro while the wound healing potential of CSLNs (incorporated in a hydrogel) was assessed in vivo. In (i) nitrogen mustard gas and (ii) a full-thickness excision wound model, CSLNs exhibited (a) significantly faster wound closure, (b) histologically and immunohistochemically better healing, (c) lower oxidative stress (LPO) and (d) inflammation (TNFα), and (e) increased angiogenesis (VEGF) and antioxidant enzymes, i.e., catalase and GSH levels. CSLNs thus offer a promising modern wound therapy especially for infected wounds, considering their effects in mature biofilm disruption.

Background Sulfur mustard (SM) is a chemical warfare vesicant that severely injures exposed eyes, lungs, and skin. Mechlorethamine hydrochloride (NM) is widely used as an SM surrogate. This study aimed to develop a depilatory double‐disc (DDD) NM skin burn model for investigating vesicant pharmacotherapy countermeasures. Methods Hair removal method (clipping only versus clipping followed by a depilatory), the effect of acetone in the vesicant administration vehicle, NM dose (0.5–20 μmol), vehicle volume (5–20 μl), and time course (0.5–21 days) were investigated using male and female CD‐1 mice. Edema, an indicator of burn response, was assessed by biopsy skin weight. The ideal NM dose to induce partial‐thickness burns was assessed by edema and histopathologic evaluation. The optimized DDD model was validated using an established reagent, NDH‐4338, a cyclooxygenase, inducible nitric oxide synthase, and acetylcholinesterase inhibitor prodrug. Results Clipping/depilatory resulted in a 5‐fold higher skin edematous response and was highly reproducible (18‐fold lower %CV) compared to clipping alone. Acetone did not affect edema formation. Peak edema occurred 24–48 h after NM administration using optimized dosing methods and volume. Ideal partial‐thickness burns were achieved with 5 μmol of NM and responded to treatment with NDH‐4338. No differences in burn edematous responses were observed between males and females. Conclusion A highly reproducible and sensitive partial‐thickness skin burn model was developed for assessing vesicant pharmacotherapy countermeasures. This model provides clinically relevant wound severity and eliminates the need for organic solvents that induce changes to the skin barrier function.