Hsueh Yuan-Shuo, Shyong Yan-Jye, Yu Hsiu-Ching, Jheng Shu-Jhen, Lin Shang-Wen, Wu Hua-Lin, Tsai Jui-Chen
Department of Medical Science Industries, College of Health Sciences, Chang Jung Christian University, Tainan 711, Taiwan.
College of Bioscience and Biotechnology, National Cheng Kung University, Tainan 701, Taiwan.
Pharmaceutics. 2021 Sep 2;13(9):1386. doi: 10.3390/pharmaceutics13091386.
Recombinant human thrombomodulin (rhTM), an angiogenesis factor, has been demonstrated to stimulate cell proliferation, keratinocyte migration and wound healing. The objective of this study was to develop nanostructured lipid carrier (NLC) formulations encapsulating rhTM for promoting chronic wound healing. RhTM-loaded NLCs were prepared and characterized. Encapsulation efficiency was more than 92%. The rate of rhTM release from different NLC formulations was influenced by their lipid compositions and was sustained for more than 72 h. Studies on diabetic mouse wound model suggested that rhTM-NLC 1.2 µg accelerated wound healing and was similar to recombinant human epidermal growth factor-NLC (rhEGF-NLC) 20 µg. By incorporating 0.085% carbopol (a highly crosslinked polyacrylic acid polymer) into rhTM NLC, the NLC-gel presented similar particle characteristics, and demonstrated physical stability, sustained release property and stability within 12 weeks. Both rhTM NLC and rhTM NLC-gel improved wound healing of diabetic mice and cell migration of human epidermal keratinocyte cell line (HaCaT) significantly. In comparison with rhTM solution, plasma concentrations of rhTM post applications of NLC and NLC-gel formulations were lower and more sustained in 24 h. The developed rhTM NLC and rhTM NLC-gel formulations are easy to prepare, stable and convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients.
重组人血栓调节蛋白（rhTM）作为一种血管生成因子，已被证明可刺激细胞增殖、角质形成细胞迁移及伤口愈合。本研究的目的是开发包封rhTM的纳米结构脂质载体（NLC）制剂，以促进慢性伤口愈合。制备并表征了载rhTM的NLC。包封率超过92%。不同NLC制剂中rhTM的释放速率受其脂质组成影响，且可持续72小时以上。对糖尿病小鼠伤口模型的研究表明，1.2μg的rhTM-NLC加速了伤口愈合，与20μg的重组人表皮生长因子-NLC（rhEGF-NLC）效果相似。通过在rhTM NLC中加入0.085%的卡波姆（一种高度交联的聚丙烯酸聚合物），NLC凝胶呈现出相似的颗粒特性，并在12周内表现出物理稳定性、缓释特性和稳定性。rhTM NLC和rhTM NLC凝胶均显著改善了糖尿病小鼠的伤口愈合及人表皮角质形成细胞系（HaCaT）的细胞迁移。与rhTM溶液相比，应用NLC和NLC凝胶制剂后rhTM的血浆浓度在24小时内较低且更持久。所开发的rhTM NLC和rhTM NLC凝胶制剂易于制备、稳定且便于应用于伤口，同时减少全身暴露，这可能为慢性伤口患者护理提供潜在的给药系统。
