Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis
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-elu...
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MDPI AG
2022-11-01
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| Series: | Pharmaceuticals |
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| Online Access: | https://www.mdpi.com/1424-8247/15/11/1358 |
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| author | Chen-Hung Lee Chien-Hao Huang Kuo-Chun Hung Shu-Chun Huang Chi-Ching Kuo Shih-Jung Liu |
| author_facet | Chen-Hung Lee Chien-Hao Huang Kuo-Chun Hung Shu-Chun Huang Chi-Ching Kuo Shih-Jung Liu |
| author_sort | Chen-Hung Lee |
| collection | DOAJ |
| description | 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, <i>p</i> < 0.001) and pore areas (3405 ± 1437 nm<sup>2</sup> vs. 8826 ± 4906 nm<sup>2</sup>, <i>p</i> < 0.001), as well as a higher hydrophilicity value (95.2 ± 2.2° vs. 113.9 ± 4.9°, <i>p</i> = 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 %, <i>p</i> < 0.001) and the level of the angiogenesis using CD31 expression (1.73 ± 0.39 vs. 0.45 ± 0.17 <i>p</i> = 0.006 for Western blot; 2.2 ± 0.5 vs. 0.7 ± 0.1, <i>p</i> < 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. |
| first_indexed | 2024-03-09T18:45:29Z |
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| id | doaj.art-d7fb15ba0a8f46f1abed8ded85113e8b |
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| language | English |
| last_indexed | 2024-03-09T18:45:29Z |
| publishDate | 2022-11-01 |
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| spelling | doaj.art-d7fb15ba0a8f46f1abed8ded85113e8b2023-11-24T06:18:40ZengMDPI AGPharmaceuticals1424-82472022-11-011511135810.3390/ph15111358Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by AngiogenesisChen-Hung Lee0Chien-Hao Huang1Kuo-Chun Hung2Shu-Chun Huang3Chi-Ching Kuo4Shih-Jung Liu5Division of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanLinkou Medical Center, Division of Hepatology, Department of Gastroenterology and Hepatology, Chang-Gung Memorial Hospital, Taoyuan 33305, TaiwanDivision of Cardiology, Department of Internal Medicine, Chang Gung Memorial Hospital-Linkou, Chang Gung University College of Medicine, Taoyuan 33302, TaiwanDepartment of Physical Medicine and Rehabilitation, Chang Gung Memorial Hospital, New Taipei Municipal Tucheng Hospital, New Taipei 23652, TaiwanResearch and Development Center of Smart Textile Technology, Institute of Organic and Polymeric Materials, National Taipei University of Technology, Taipei 10608, TaiwanBone and Joint Research Center, Department of Orthopedic Surgery, Chang Gung Memorial Hospital-Linkou, Taoyuan 33305, TaiwanThe 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, <i>p</i> < 0.001) and pore areas (3405 ± 1437 nm<sup>2</sup> vs. 8826 ± 4906 nm<sup>2</sup>, <i>p</i> < 0.001), as well as a higher hydrophilicity value (95.2 ± 2.2° vs. 113.9 ± 4.9°, <i>p</i> = 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 %, <i>p</i> < 0.001) and the level of the angiogenesis using CD31 expression (1.73 ± 0.39 vs. 0.45 ± 0.17 <i>p</i> = 0.006 for Western blot; 2.2 ± 0.5 vs. 0.7 ± 0.1, <i>p</i> < 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.https://www.mdpi.com/1424-8247/15/11/1358vildagliptinnanofibrous membraneselectrospinningrelease characteristicsdiabetic wound healing |
| spellingShingle | Chen-Hung Lee Chien-Hao Huang Kuo-Chun Hung Shu-Chun Huang Chi-Ching Kuo Shih-Jung Liu Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis Pharmaceuticals vildagliptin nanofibrous membranes electrospinning release characteristics diabetic wound healing |
| title | Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis |
| title_full | Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis |
| title_fullStr | Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis |
| title_full_unstemmed | Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis |
| title_short | Nanofibrous Vildagliptin/PLGA Membranes Accelerate Diabetic Wound Healing by Angiogenesis |
| title_sort | nanofibrous vildagliptin plga membranes accelerate diabetic wound healing by angiogenesis |
| topic | vildagliptin nanofibrous membranes electrospinning release characteristics diabetic wound healing |
| url | https://www.mdpi.com/1424-8247/15/11/1358 |
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