Temporal pressure enhanced topical drug delivery through micropore formation
Transdermal drug delivery uses chemical, physical, or biochemical enhancers to cross the skin barrier. However, existing platforms require high doses of chemical enhancers or sophisticated equipment, use fragile biomolecules, or are limited to a certain type of drug. Here, we report an innovative me...
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sg-ntu-dr.10356-1454022023-12-29T06:53:59Z Temporal pressure enhanced topical drug delivery through micropore formation Lio, Daniel Chin Shiuan Chia, Ruining Kwek, Milton Sheng Yi Wiraja, Christian Madden, Leigh Edward Chang, Hao S. Mohideen Abdul Khadir Wang, Xiaomeng Becker, David Lawrence Xu, Chenjie School of Chemical and Biomedical Engineering Interdisciplinary Graduate School (IGS) Lee Kong Chian School of Medicine (LKCMedicine) NTU Institute for Health Technologies Science::Medicine Chemical Equipment Drug Dosage Transdermal drug delivery uses chemical, physical, or biochemical enhancers to cross the skin barrier. However, existing platforms require high doses of chemical enhancers or sophisticated equipment, use fragile biomolecules, or are limited to a certain type of drug. Here, we report an innovative methodology based on temporal pressure to enhance the penetration of all kinds of drugs, from small molecules to proteins and nanoparticles (up to 500 nm). The creation of micropores (~3 μm2) on the epidermal layer through a temporal pressure treatment results in the elevated expression of gap junctions, and reduced expression of occludin tight junctions. A 1 min treatment of 0.28-MPa allows nanoparticles (up to 500 nm) and macromolecules (up to 20 kDa) to reach a depth of 430-μm into the dermal layer. Using, as an example, the delivery of insulin through topical application after the pressure treatment yields up to 80% drop in blood glucose in diabetic mice. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) Skin Research Institute of Singapore (SRIS) Published version C.X. acknowledges the funding support from Singapore Agency for Science, Technology and Research (A*STAR) Science and Engineering Research Council Additive Manufacturing for Biological Materials (AMBM) program (A18A8b0059) and internal grant from City University of Hong Kong (#9610472). D.L.B. acknowledges the funding support from A*STAR under its Industry Alignment Fund–Pre-Positioning Programme (IAF-PP): (1) Wound Care Innovation for the Tropics Programme, Singapore (WCIT): (H18/01/a0/0I9) and (H17/01/a0/0C9); (2) The Skin Research Institute of Singapore, Phase 2: SRIS@Novena (“IAF-PP SRIS2 Grant”, H17/01/a0/004). X.W. acknowledges the funding support from the National Medical Research Council Singapore Large Collaborative Grant DYNAMO (NMRC/OFLCG/001/2017); and National Medical Research Council Singapore Large Collaborative Grant TAAP (NMRC/OFLCG/004/2018). 2020-12-21T04:00:17Z 2020-12-21T04:00:17Z 2020 Journal Article Lio, D. C. S., Chia, R., Kwek, M. S. Y., Wiraja, C., Madden, L. E., Chang, H., . . . Xu, C. (2020). Temporal pressure enhanced topical drug delivery through micropore formation. Science Advances, 6(22), eaaz6919-. doi:10.1126/sciadv.aaz6919 2375-2548 https://hdl.handle.net/10356/145402 10.1126/sciadv.aaz6919 32523993 22 6 en A18A8b0059 H18/01/a0/0I9 H17/01/a0/0C9 H17/01/a0/004 NMRC/OFLCG/001/2017 NMRC/OFLCG/004/2018 Science Advances © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC). application/pdf |
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Science::Medicine Chemical Equipment Drug Dosage Lio, Daniel Chin Shiuan Chia, Ruining Kwek, Milton Sheng Yi Wiraja, Christian Madden, Leigh Edward Chang, Hao S. Mohideen Abdul Khadir Wang, Xiaomeng Becker, David Lawrence Xu, Chenjie Temporal pressure enhanced topical drug delivery through micropore formation |
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Transdermal drug delivery uses chemical, physical, or biochemical enhancers to cross the skin barrier. However, existing platforms require high doses of chemical enhancers or sophisticated equipment, use fragile biomolecules, or are limited to a certain type of drug. Here, we report an innovative methodology based on temporal pressure to enhance the penetration of all kinds of drugs, from small molecules to proteins and nanoparticles (up to 500 nm). The creation of micropores (~3 μm2) on the epidermal layer through a temporal pressure treatment results in the elevated expression of gap junctions, and reduced expression of occludin tight junctions. A 1 min treatment of 0.28-MPa allows nanoparticles (up to 500 nm) and macromolecules (up to 20 kDa) to reach a depth of 430-μm into the dermal layer. Using, as an example, the delivery of insulin through topical application after the pressure treatment yields up to 80% drop in blood glucose in diabetic mice. |
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School of Chemical and Biomedical Engineering |
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School of Chemical and Biomedical Engineering Lio, Daniel Chin Shiuan Chia, Ruining Kwek, Milton Sheng Yi Wiraja, Christian Madden, Leigh Edward Chang, Hao S. Mohideen Abdul Khadir Wang, Xiaomeng Becker, David Lawrence Xu, Chenjie |
format |
Article |
author |
Lio, Daniel Chin Shiuan Chia, Ruining Kwek, Milton Sheng Yi Wiraja, Christian Madden, Leigh Edward Chang, Hao S. Mohideen Abdul Khadir Wang, Xiaomeng Becker, David Lawrence Xu, Chenjie |
author_sort |
Lio, Daniel Chin Shiuan |
title |
Temporal pressure enhanced topical drug delivery through micropore formation |
title_short |
Temporal pressure enhanced topical drug delivery through micropore formation |
title_full |
Temporal pressure enhanced topical drug delivery through micropore formation |
title_fullStr |
Temporal pressure enhanced topical drug delivery through micropore formation |
title_full_unstemmed |
Temporal pressure enhanced topical drug delivery through micropore formation |
title_sort |
temporal pressure enhanced topical drug delivery through micropore formation |
publishDate |
2020 |
url |
https://hdl.handle.net/10356/145402 |
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1787136802232991744 |