Abstract

Curcumin, an excellent anti-inflammatory, anti-infectious, antioxidant, and angiogenesis-promoting agent, holds immense potential for treating chronic wounds. However, rapid metabolism, low solubility, low permeability, and toxicity at higher concentrations hinder its therapeutic efficacy. The current therapeutic alternatives are inefficient in healing chronic wounds and often lead to severe infection, amputation, and mortality. There is a dire need for a novel therapeutic drug delivery system to address the challenges associated with chronic wounds. Nanotechnology holds immense potential to aid wound healing by improving permeability, bioavailability, and solubility; preventing degradation in the chronic wound microenvironment, and increasing the therapeutic potential of the drug. The research aimed to develop and optimize curcumin-incorporated nanostructured lipid carriers (CUR-NLCs) with high entrapment efficiency, improved stability, prolonged drug release profile, and particle size suitable for wound healing (100–200 nm). This work differs from previously reported CUR-NLCs, as systematic optimization is performed for CUR-NLCs fabricated using the high-pressure homogenization (HPH) technique. HPH offers unique advantages of scalability, reproducibility, high drug entrapment, solvent-free preparation, and narrow particle size distribution. The CUR-NLCs were optimized by applying a Box–Behnken design (3 factors, 3 levels) utilizing drug concentration, co-surfactant concentration, and high-speed homogenizer speed as independent variables and particle size, entrapment efficiency, and drug loading as dependent variables. The optimized CUR-NLCs identified using the desirability approach (D = 1) had a particle size of 145.2 ± 1.3 nm, a polydispersity index of 0.233 ± 0.06, a zeta potential of −30.4 ± 2.8 mV, and a good entrapment efficiency of 81.64% ± 2.0%. The in vitro drug release studies depicted a prolonged release of CUR up to 48 hours, which will help to target the inflammatory phase of wound healing, prevent chronic inflammation, and accelerate the transition to the proliferation phase. The release kinetics results indicated that the Weibull model provided the best fit (R2 = 0.994), explaining the combined diffusion and dissolution-dependent drug release. The optimized CUR-NLCs were stable under varied storage conditions. The research findings demonstrate that the optimized CUR-NLCs could be further employed as a promising alternative for chronic wound management.

Key words: Curcumin, Wound healing, Nanostructured lipid carriers, Box-behnken design, Weibull kinetics