Development of Curcumin-loaded Nanocomposite Hydrogels for Wound Healing

Abstract

Efforts to improve wound healing outcomes have led to research on novel dressings. This study focuses on developing curcumin-embedded nanocomposite hydrogels for the efficient delivery of curcumin (Cur) in wound healing. Although Cur has potent healing properties, its poor aqueous solubility hinders its effectiveness. To address this, curcumin nanosuspension (Cur-NS) and curcumin liposome (Cur-L) formulations were optimized using the Box-Behnken design to enhance particle size, size distribution, zeta potential, and Cur content. The optimized nano-Curs were then evaluated for morphology, drug release profile, cytotoxicity, and healing efficacy based on antioxidant and cell migration effects. The amorphization of Cur-NS was assessed through its thermal properties, crystallinity, and stability. The hydrogel formulations were optimized using a simplex centroid mixture design and a central composite design. Cur-NS was incorporated into genipin-crosslinked chitosan-polyvinylpyrrolidone (CS-PVP) hydrogel, while a polyvinylpyrrolidone-co-itaconic acid (PNVP-ITA) copolymer was synthesized to enhance the properties of the hydrogel containing hyaluronic acid (HA), polyvinyl alcohol (PVA), and Cur-L embedded into the HA/PVA/PNVP-ITA hydrogel. Interactions between hydrogels and nano-Curs were assessed using Fourier-transform infrared spectroscopy (FTIR). Their drug release kinetics were studied, and in vivo, skin recovery was investigated on incisional wounds of the Wistar rat model. The optimized Cur-NS, containing 2% Tween® 20, 4.97% Pluronic® F127, and 1 mg/mL Cur, yielded stable nano-sized particles with a slight negative charge and a Cur content of 1.16 ± 0.03 mg/mL. Cur-NS (5% w/w of polymers) was incorporated into the optimized hydrogels containing 70% CS and 30% PVP, achieving 97.54 ± 4.54% loading efficiency. Meanwhile, the optimized liposomes were constructed from 2.7% Tween® 20, 0.04% oleic acid, and 8.1% Cur, yielding negatively charged particles with a narrow size distribution and a Cur content of 19.92 ± 0.54 µg/mg. The optimized hydrogel contained 5% HA and 10% PVA, with properties improved by adding synthesized PNVP-ITA. Cur-L (0.5% w/w of polymers) was successfully integrated into the HA/PVA/PNVP-ITA hydrogel via absorption with an efficiency of 95.22 ± 4.24%. Nano-Curs enhanced its antioxidant effect in an aqueous medium by improving its solubility. Both Cur-NSs and Cur-Ls were released from the hydrogel matrix via diffusion-erosion and diffusion-controlled mechanisms, following the Korsmeyer-Peppas model. These hydrogels were safe for normal human fibroblast (NHF) cells and induced skin recovery faster than a commercial patch within 5 days. Overall, this study offers a promising solution for wound care.

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