He Jingyu, Wang Chen, Lin Gan, Xia Xiao, Chen Hangping, Feng Zhiyuan, Huang Zhengwei, Pan Xin, Zhang Xuejuan, Wu Chuanbin, Huang Ying
College of Pharmacy, Jinan University, Guangzhou 511443, Guangdong, PR China.
School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, Guangdong, PR China.
Int J Pharm. 2023 Nov 5;646:123442. doi: 10.1016/j.ijpharm.2023.123442. Epub 2023 Sep 27.
The diabetic wound is a prevalent and serious complication of diabetes, which easily deteriorates due to susceptibility to infection and difficulty in healing, causing a high risk of amputation and economic burden to patients. Bacterial infection, persistent excessive inflammation, and cellular and angiogenesis disorders are the main reasons for the difficulty of diabetic wound healing. In this study, glycerol monooleate (GMO) was used to prepare lyotropic liquid crystal hydrogel (LLC) containing the natural antimicrobial peptide LL37 and carbenoxolone (CBX) to achieve antibacterial, anti-inflammation, and healing promotion for the treatment of diabetic wounds. The shear-thinning properties of the LLC precursor solution allowed it to be administered in the form of a spray, which perfectly fitted the shape of the wound and transformed into a gel after absorbing wound exudate to act as a wound protective barrier. The faster release of LL37 realized rapid sterilization of wounds, controlled the source of inflammation, and accelerated wound healing. The inflammatory signaling pathway was blocked by the subsequently released CBX, and the spread of the inflammatory response was inhibited and then further weakened. In addition, CBX down-regulated connexin (Cx43) to assist LL37 to promote cell migration and proliferation better. Combined with the pro-angiogenic effect of LL37, the healing of diabetic wounds was significantly accelerated. All these advantages made LL37-CBX-LLC a promising approach for the treatment of chronic diabetic wounds.
糖尿病伤口是糖尿病常见且严重的并发症，由于易受感染且愈合困难，容易恶化，给患者带来高截肢风险和经济负担。细菌感染、持续性过度炎症以及细胞和血管生成紊乱是糖尿病伤口愈合困难的主要原因。在本研究中，使用甘油单油酸酯（GMO）制备了含有天然抗菌肽LL37和甘草次酸（CBX）的溶致液晶水凝胶（LLC），以实现抗菌、抗炎和促进愈合，用于治疗糖尿病伤口。LLC前体溶液的剪切变稀特性使其能够以喷雾形式给药，完美贴合伤口形状，并在吸收伤口渗出液后转变为凝胶，充当伤口保护屏障。LL37的更快释放实现了伤口的快速杀菌，控制了炎症源，并加速了伤口愈合。随后释放的CBX阻断了炎症信号通路，抑制并进一步减弱了炎症反应的扩散。此外，CBX下调连接蛋白（Cx43），以协助LL37更好地促进细胞迁移和增殖。结合LL37的促血管生成作用，显著加速了糖尿病伤口的愈合。所有这些优点使LL37-CBX-LLC成为治疗慢性糖尿病伤口的一种有前景的方法。
