@article{80046100145446fba8e85a557b3b4be8,
title = "Nanostructured lipid carrier gel formulation of recombinant human thrombomodulin improve diabetic wound healing by topical administration",
abstract = "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 com-parison 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.",
author = "Yuan-Shuo Hsueh and Shyong, {Yan Jye} and Yu, {Hsiu Ching} and Jheng, {Shu Jhen} and Lin, {Shang Wen} and Wu, {Hua Lin} and Tsai, {Jui Chen}",
note = "Funding Information: eFvigeurr, ehSa2v:inRgh hTMighr ecloenasceenptrroafitlieonfr oomf thNeLsCe gfroormwuthla ftaiocntos,rsF iegnutreeriSn3g: tWhoeu cnirdcuclloastiuorne m%aoyf crhaTuMse concerns such as risk of cancer. Both treatments with rhTM NLC 1.2 µg and rhTM NLC-gel 1.2 µg increased granulation tissues and re-epithelialization, and induced angiogenesis in the granulation tissue, leading to improvement of chronic wound healing. In addition, when compared with solution form, plasma concentrations of rhTM post applica-Vtiiosnusa loizfa NtioLnC. Ya.-nJd.S .N: CLoCn-cgeeplt ufoalrimzautiloanti,oDnastawceurrea tlioown,eWr raintidng m—oorreig sinuasltadirnaeftd. Hin. -2C4.Yh.:, Iwnvheiscthi- lgiakteiolyn,rDesautalticnugra itniolno.nSg.e-Jr.J .t:reInatvmesetingta ttiiomne,.D Tahtae cduervateiloonp.eSd. -rWh.TLM.: M NeLthCo daonldogryh,TVMisuNalLizCat-igoenl. formulations are stable, easy to prepare, convenient to apply to the wound with reduced systemic exposure, which may warrant potential delivery systems for the care of chronic wound patients. The gel form with slight viscosity may be more advantageous for topical aFupnpdliicnagt:ioTnh.is research was supported by the Ministry of Science and Technology, Taiwan (MOST 109-2635-B-006-001; MOST 109-2314-B-309-002; MOST 110-2314-B-309-001) and the Headquarters Funding Information: This research was supported by the Ministry of Science and Technology, Taiwan (MOST 109-2635-B-006-001; MOST 109-2314-B-309-002; MOST 110-2314-B-309-001) and the Headquarters Supplementary Materials: The following are available online at www.mdpi.com/xxx/s1, Figure S1: Characteristics of NLC formulations in 3D bar graph, Figure S2: RhTM release profile from NLC. Funding Information: of University Advancement to the National Cheng Kung University, which was sponsored by the Ministry of Education, Taiwan, R.O.C. [grant numbers D107-F2518 and D108-F2506]. Publisher Copyright: {\textcopyright} 2021 by the authors. Licensee MDPI, Basel, Switzerland.",
year = "2021",
month = sep,
doi = "10.3390/pharmaceutics13091386",
language = "English",
volume = "13",
journal = "Pharmaceutics",
issn = "1999-4923",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "9",
}