Lee Chen-Hung, Huang Chien-Hao, Hung Kuo-Chun, Huang Shu-Chun, Kuo Chi-Ching, Liu Shih-Jung
Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Taoyuan 33302, Taiwan.
Linkou Medical Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Taoyuan 33305, Taiwan.
Pharmaceuticals (Basel). 2022 Nov 4;15(11):1358. doi: 10.3390/ph15111358.
The inhibition of dipeptidyl peptidase-4 (DPP4) significantly enhances the wound closure rate in diabetic patients with chronic foot ulcers. DPP4 inhibitors are only prescribed for enteral, but topical administration, if feasible, to a wound would have more encouraging outcomes. Nanofibrous drug-eluting poly-D-L-lactide-glycolide (PLGA) membranes that sustainably release a high concentration of vildagliptin were prepared to accelerate wound healing in diabetes. Solutions of vildagliptin and PLGA in hexafluoroisopropanol were electrospun into nanofibrous biodegradable membranes. The concentration of the drug released in vitro from the vildagliptin-eluting PLGA membranes was evaluated, and it was found that effective bioactivity of vildagliptin can be discharged from the nanofibrous vildagliptin-eluting membranes for 30 days. Additionally, the electrospun nanofibrous PLGA membranes modified by blending with vildagliptin had smaller fiber diameters (336.0 ± 69.1 nm vs. 743.6 ± 334.3 nm, p < 0.001) and pore areas (3405 ± 1437 nm2 vs. 8826 ± 4906 nm2, p < 0.001), as well as a higher hydrophilicity value (95.2 ± 2.2° vs. 113.9 ± 4.9°, p = 0.004), and showed a better water-retention ability within 24 h compared with PLGA membranes. The vildagliptin-eluting PLGA membrane also enhanced the diabetic wound closure rate for two weeks (11.4 ± 3.0 vs. 18.7 ± 2.6 %, p < 0.001) and the level of the angiogenesis using CD31 expression (1.73 ± 0.39 vs. 0.45 ± 0.17 p = 0.006 for Western blot; 2.2 ± 0.5 vs. 0.7 ± 0.1, p < 0.001 for immunofluorescence). These results demonstrate that nanofibrous drug-eluting PLGA membranes loaded with vildagliptin are an effective agent for sustained drug release and, therefore, for accelerating cutaneous wound healing in the management of diabetic wounds.
抑制二肽基肽酶 -4（DPP4）可显著提高患有慢性足部溃疡的糖尿病患者的伤口愈合率。DPP4抑制剂目前仅用于肠道给药，但如果可行的话，局部给药于伤口可能会有更令人鼓舞的结果。制备了可持续释放高浓度维格列汀的纳米纤维药物洗脱聚 -D -L -丙交酯 -乙交酯（PLGA）膜，以加速糖尿病患者的伤口愈合。将维格列汀和PLGA在六氟异丙醇中的溶液进行电纺丝制成纳米纤维可生物降解膜。评估了维格列汀洗脱PLGA膜在体外释放的药物浓度，发现维格列汀的有效生物活性可从纳米纤维维格列汀洗脱膜中释放30天。此外，与维格列汀共混改性的电纺纳米纤维PLGA膜具有更小的纤维直径（336.0±69.1nm对743.6±334.3nm，p<0.001）和孔隙面积（3405±1437nm²对8826±4906nm²，p<0.001），以及更高的亲水性值（95.2±2.2°对113.9±4.9°，p = 0.004），并且与PLGA膜相比，在24小时内显示出更好的保水能力。维格列汀洗脱PLGA膜还在两周内提高了糖尿病伤口的愈合率（11.4±3.0对18.7±2.6%，p<0.001），并使用CD31表达提高了血管生成水平（蛋白质印迹法为1.73±0.39对0.45±0.17，p = 0.006；免疫荧光法为2.2±0.5对0.7±0.1，p<0.001）。这些结果表明，负载维格列汀的纳米纤维药物洗脱PLGA膜是一种有效的持续药物释放剂，因此可用于加速糖尿病伤口管理中的皮肤伤口愈合。
