Chitosan/Alginate Nanoparticles with Sustained Release of Esculentoside A for Burn Wound Healing

Burn injury remains one of the most devastating burdens on global public health. The inflammation, caused by burn injury and transplantation of dermal scaffolds, often leads to delayed burn wound healing. Esculentoside A (EsA), with a strong anti-inflammatory capacity, is an available agent that might contribute to the treatment of burn wounds. However, the poor stability and toxicity of EsA limit its clinical application. In the present study, we constructed chitosan/alginate nanoparticles (EsA-CS/ALG-NPs) to improve sustainability and reduce toxicity followed by impregnation of the prepared EsA-CS/ALG-NPs into a collagen/chitosan scaffold (EsA-CS/ALG-NPs@CCS). The particle size, structural morphology, thermal properties, and chemical interaction of repaired nanoparticles were evaluated using the Nanometrics instrument, differential scanning calorimetry, transmission electron microscopy, and Fourier transform infrared spectroscopy, respectively. The hybrid EsA-CS/ALG-NPs@CCS was evaluated for physical characteristics, in vitro drug release, biocompatibility, and anti-inflammation capacity with RAW 264.7 cells and in vivo burn wound healing studies with SD rats. The results showed that we successfully constructed CS/ALG-NPs and optimized the preparation process to achieve the highest encapsulation efficiency. The hybrid EsA-CS/ALG-NPs@CCS, with reduced cytotoxicity and sustained release of EsA, could alleviate inflammation, decrease the ratio of M1 macrophages, and increase the proportion of M2 macrophages in vitro. It was demonstrated that 5 μg EsA CS/ALG-NPs@CCS not only reduces inflammatory cytokines secretion and inhibits M1 macrophages but also promotes the release of anti-inflammatory cytokines and activates M2 macrophages, thereby achieving accelerated and high-quality healing of burn wounds ultimately. In summary, our work suggests that the synergistic combination of EsA, nanoparticles, and scaffolds provided a promising strategy for treating burn injuries.