Lapmanee Sarawut, Bhubhanil Sakkarin, Charoenphon Natthawut, Inchan Anjaree, Bunwatcharaphansakun Phichaporn, Khongkow Mattaka, Namdee Katawut
Chulabhorn International College of Medicine, Thammasat University, Pathumthani 10120, Thailand.
Department of Basic Medical Sciences, Faculty of Medicine, Siam University, Bangkok 10160, Thailand.
Gels. 2024 Dec 20;10(12):843. doi: 10.3390/gels10120843.
Chronic wounds represent a persistent clinical challenge due to prolonged inflammation and impaired tissue repair mechanisms. Cannabidiol (CBD), recognized for its anti-inflammatory and pro-healing properties, shows therapeutic promise in wound care. However, its delivery via lipid nanoparticles (LNPs) remains challenging due to CBD's inherent instability and low bioavailability. This study developed and characterized a novel hydrogel scaffold composed of CBD-loaded LNPs (CBD/LNPs) integrated into a polyvinyl alcohol (PVA) and sodium alginate (SA) matrix, designed to enhance wound repair and mitigate inflammation. The characteristics of the hydrogel scaffold were observed including the degree of swelling and LNPs' release profiles. Furthermore, in the results, CBD/LNPs displayed enhanced stability and reduced cytotoxicity compared to unencapsulated CBD. In vitro assays demonstrated that CBD/LNPs significantly promoted fibroblast migration in gap-closure wound models and reduced intracellular reactive oxygen species, supporting their potential as a biocompatible and efficacious agent for cellular repair and oxidative stress attenuation. In vivo experiments using adult male Wistar rats with aseptic cutaneous wounds revealed that treatment with CBD/LNP-PVA/SA hydrogel scaffold significantly accelerated wound closure relative to blank hydrogel controls, demonstrating a substantial reduction in the wound area over time. Histological analysis confirms notable improvements in skin morphology in wounds treated with CBD/LNP-PVA/SA hydrogel scaffold with evidence of accelerated epithelialization, enhanced collagen deposition, and increased dermal thickness and vascularization. Additionally, skin histology showed a more organized epidermal layer and reduced inflammatory cell infiltration in CBD/LNP-PVA/SA hydrogel scaffold-treated wounds, corresponding to a 35% increase in the wound closure rate by day 28 post-treatment. These findings suggest that CBD/LNP-PVA/SA hydrogel scaffolds facilitate inflammation resolution and structural wound healing through localized, sustained CBD delivery. The dual anti-inflammatory and wound-healing effects position CBD/LNP-PVA/SA hydrogel scaffold as a promising approach for chronic wound management. Future investigations are warranted to elucidate the mechanistic pathways by which CBD modulates the skin architecture and to explore its translational applications in clinical wound care.
由于炎症持续时间长和组织修复机制受损，慢性伤口是一个持续存在的临床挑战。大麻二酚（CBD）因其抗炎和促进愈合的特性而闻名，在伤口护理中显示出治疗前景。然而，由于CBD固有的不稳定性和低生物利用度，通过脂质纳米颗粒（LNP）递送它仍然具有挑战性。本研究开发并表征了一种新型水凝胶支架，该支架由负载CBD的LNP（CBD/LNP）整合到聚乙烯醇（PVA）和海藻酸钠（SA）基质中组成，旨在促进伤口修复并减轻炎症。观察了水凝胶支架的特性，包括溶胀程度和LNP的释放曲线。此外，结果显示，与未封装的CBD相比，CBD/LNP表现出增强的稳定性和降低的细胞毒性。体外试验表明，CBD/LNP在间隙闭合伤口模型中显著促进成纤维细胞迁移，并减少细胞内活性氧，支持其作为细胞修复和氧化应激减轻的生物相容性和有效剂的潜力。使用成年雄性Wistar大鼠进行无菌皮肤伤口的体内实验表明，与空白水凝胶对照相比，用CBD/LNP-PVA/SA水凝胶支架治疗显著加速了伤口闭合，表明随着时间的推移伤口面积大幅减少。组织学分析证实，用CBD/LNP-PVA/SA水凝胶支架治疗的伤口皮肤形态有显著改善，有上皮化加速、胶原沉积增强、真皮厚度和血管化增加的证据。此外，皮肤组织学显示，在CBD/LNP-PVA/SA水凝胶支架治疗的伤口中，表皮层更有组织，炎症细胞浸润减少，与治疗后第28天伤口闭合率提高35%相对应。这些发现表明，CBD/LNP-PVA/SA水凝胶支架通过局部、持续的CBD递送促进炎症消退和伤口结构愈合。抗炎和伤口愈合的双重作用使CBD/LNP-PVA/SA水凝胶支架成为慢性伤口管理的一种有前途的方法。未来有必要进行研究，以阐明CBD调节皮肤结构的机制途径，并探索其在临床伤口护理中的转化应用。
