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.
Keywords: TNFα; VEGF; biofilm; nanocarriers; oxidative stress; safety; wound closure.