Lin Qian, Zhu Fucheng, Shiye Aji, Liu Runyu, Wang Xiaolan, Ye Zi, Ding Yinhuan, Sun Xiaolei, Ma Yarong
Department of General Surgery (Vascular Surgery), the Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People's Republic of China.
Department of Hepatobiliary Pancreatic Vascular Surgery, the Second Affiliated Hospital of Chengdu Medical College, Chengdu, 610057, People's Republic of China.
Int J Nanomedicine. 2024 Dec 3;19:12835-12850. doi: 10.2147/IJN.S488115. eCollection 2024.
Diabetic wounds are serious chronic complications of diabetes and can lead to amputation and death. Although considerable progress has been made in drugs and materials for treating it, it's still an urgent clinical problem as the materials and drugs have potential therapeutic drawbacks, such as low delivery efficiency and poor tissue permeability. To promote diabetic wound healing, a composite of thonningianin A (TA)-loaded chitosan nanoparticles (CNPS) encapsulated by a Pluronic F-127 (PF-127) hydrogel (TA-CNPS-PF) was developed in this study.
TA-CNPS was prepared by ionic gelation method and TA-CNPS was thoroughly dispersed into PF-127 hydrogel to prepare TA-CNPS-PF. The particle size, hydrogel structure, encapsulation ratio, release ratio, antimicrobial properties of TA-CNPS-PF were determined and the effect of TA-CNPS-PF on diabetic wounds was assessed. The effect of TA on macrophage polarization was also examined in vitro.
The particle size was approximately 100 nm of TA-CNPS-PF and the hydrogel had a homogeneous three-dimensional reticulation structure. The encapsulation efficiency of TA in the CNPS were 99.3% and the release ratio of TA-CNPS-PF was approximately 86% and has antimicrobial properties. TA-CNPS-PF promoted diabetic wound healing significantly. Histopathology confirmed that TA-CNPS-PF promoted complete re-epithelialization and adequate collagen deposition. TA promoted the polarization of M1 macrophages into M2 macrophages via light microscopy, immunocytometry and flow cytometry. TA-CNPS-PF also promoted an increase in the number of M2 macrophages in diabetic wounds.
TA promotes diabetic wound healing by promoting the polarization of M1 macrophages into M2 macrophages and TA-CNPS-PF has good antimicrobial activity and a good drug release ratio in this study, which provides a new direction for the treatment of diabetic wounds and is expected to be highly advantageous in clinical diabetes wound therapy.
糖尿病伤口是糖尿病严重的慢性并发症，可导致截肢和死亡。尽管在治疗糖尿病伤口的药物和材料方面取得了相当大的进展，但由于材料和药物存在潜在的治疗缺陷，如递送效率低和组织渗透性差，这仍然是一个紧迫的临床问题。为促进糖尿病伤口愈合，本研究制备了一种由泊洛沙姆F-127（PF-127）水凝胶包裹的载有托宁宁A（TA）的壳聚糖纳米粒（CNPS）复合物（TA-CNPS-PF）。
采用离子凝胶法制备TA-CNPS，并将其充分分散到PF-127水凝胶中制备TA-CNPS-PF。测定TA-CNPS-PF的粒径、水凝胶结构、包封率、释放率、抗菌性能，并评估TA-CNPS-PF对糖尿病伤口的影响。同时在体外研究TA对巨噬细胞极化的影响。
TA-CNPS-PF的粒径约为100nm，水凝胶具有均匀的三维网状结构。TA在CNPS中的包封效率为99.3%，TA-CNPS-PF的释放率约为86%，且具有抗菌性能。TA-CNPS-PF显著促进糖尿病伤口愈合。组织病理学证实TA-CNPS-PF促进了完全的上皮再形成和足够的胶原蛋白沉积。通过光学显微镜、免疫细胞化学和流式细胞术证实TA促进M1巨噬细胞向M2巨噬细胞极化。TA-CNPS-PF还促进糖尿病伤口中M2巨噬细胞数量增加。
TA通过促进M1巨噬细胞向M2巨噬细胞极化来促进糖尿病伤口愈合，且在本研究中TA-CNPS-PF具有良好的抗菌活性和药物释放率，为糖尿病伤口治疗提供了新方向，有望在临床糖尿病伤口治疗中具有很大优势。
