A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis
Microcirculation damage, dermal thickening, and difficulty in the spatiotemporal coordination of key platelet factor 4 (CXCL4) and transforming growth factor-β (TGF-β) contribute to the lack of effective treatments for systemic sclerosis (scleroderma, SSc). To address these challenges, we proposed a...
Saved in:
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-05-01
|
| Series: | Gels |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2310-2861/11/6/384 |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1839653938119311360 |
|---|---|
| author | Yuanyuan Wang Caiyun Zhong Kexin Wang Shihong Shen Daidi Fan |
| author_facet | Yuanyuan Wang Caiyun Zhong Kexin Wang Shihong Shen Daidi Fan |
| author_sort | Yuanyuan Wang |
| collection | DOAJ |
| description | Microcirculation damage, dermal thickening, and difficulty in the spatiotemporal coordination of key platelet factor 4 (CXCL4) and transforming growth factor-β (TGF-β) contribute to the lack of effective treatments for systemic sclerosis (scleroderma, SSc). To address these challenges, we proposed a novel synergistic drug combination of ginsenoside Rk3 (CXCL4 regulator) and metformin (Met, TGF-β regulator) based on molecular docking and developed an ultra-long release, dual-target regulation hydrogel microneedle system (Rk3/Met URS MN). The rapidly dissolving tips of this hydrogel microneedle consisted of polyvinyl alcohol and polyvinylpyrrolidone, and were loaded with polydopamine-coated, coordination-induced self-assembled Rk3/Met nanomedicines. These micro-tips could spatiotemporally synchronize transdermal delivery of the hydrophobic Rk3 and hydrophilic Met, providing ultra-long release for up to 10 days with a single administration. The recombinant collagen CF-1552/oxidized pullulan-based (CAOP) hydrogel backing exhibited skin self-adhesiveness and excellent mechanical properties and could perform localized moisture retention and free radical scavenging at the lesion site. In vitro and in vivo efficacy studies, along with bioinformatics analysis of RNA sequencing, demonstrated that the Rk3/Met URS MN achieved immune modulation, anti-inflammatory effects, angiogenesis promotion, and antifibrosis in SSc through synergistic CXCL4/TGF-β dual-target regulation. Notably, on the 10th day, the dermal thickness decreased from 248.97 ± 21.3 μm to 152.7 ± 18.1 μm, with no significant difference from the normal group, indicating its significant potential in clinical applications in SSc. |
| format | Article |
| id | doaj-art-f59f78c9c9e04c68aa2b039f00b2e5db |
| institution | Matheson Library |
| issn | 2310-2861 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Gels |
| spelling | doaj-art-f59f78c9c9e04c68aa2b039f00b2e5db2025-06-25T13:53:36ZengMDPI AGGels2310-28612025-05-0111638410.3390/gels11060384A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic SclerosisYuanyuan Wang0Caiyun Zhong1Kexin Wang2Shihong Shen3Daidi Fan4Engineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi’an 710127, ChinaEngineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi’an 710127, ChinaEngineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi’an 710127, ChinaEngineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi’an 710127, ChinaEngineering Research Center of Western Resource Innovation Medicine Green Manufacturing, Ministry of Education, School of Chemical Engineering, Northwest University, Xi’an 710127, ChinaMicrocirculation damage, dermal thickening, and difficulty in the spatiotemporal coordination of key platelet factor 4 (CXCL4) and transforming growth factor-β (TGF-β) contribute to the lack of effective treatments for systemic sclerosis (scleroderma, SSc). To address these challenges, we proposed a novel synergistic drug combination of ginsenoside Rk3 (CXCL4 regulator) and metformin (Met, TGF-β regulator) based on molecular docking and developed an ultra-long release, dual-target regulation hydrogel microneedle system (Rk3/Met URS MN). The rapidly dissolving tips of this hydrogel microneedle consisted of polyvinyl alcohol and polyvinylpyrrolidone, and were loaded with polydopamine-coated, coordination-induced self-assembled Rk3/Met nanomedicines. These micro-tips could spatiotemporally synchronize transdermal delivery of the hydrophobic Rk3 and hydrophilic Met, providing ultra-long release for up to 10 days with a single administration. The recombinant collagen CF-1552/oxidized pullulan-based (CAOP) hydrogel backing exhibited skin self-adhesiveness and excellent mechanical properties and could perform localized moisture retention and free radical scavenging at the lesion site. In vitro and in vivo efficacy studies, along with bioinformatics analysis of RNA sequencing, demonstrated that the Rk3/Met URS MN achieved immune modulation, anti-inflammatory effects, angiogenesis promotion, and antifibrosis in SSc through synergistic CXCL4/TGF-β dual-target regulation. Notably, on the 10th day, the dermal thickness decreased from 248.97 ± 21.3 μm to 152.7 ± 18.1 μm, with no significant difference from the normal group, indicating its significant potential in clinical applications in SSc.https://www.mdpi.com/2310-2861/11/6/384systemic sclerosishydrogel microneedleCXCL4/TGF-βultra-long releasereverse skin phenotype |
| spellingShingle | Yuanyuan Wang Caiyun Zhong Kexin Wang Shihong Shen Daidi Fan A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis Gels systemic sclerosis hydrogel microneedle CXCL4/TGF-β ultra-long release reverse skin phenotype |
| title | A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis |
| title_full | A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis |
| title_fullStr | A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis |
| title_full_unstemmed | A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis |
| title_short | A Self-Adhesive Ginsenoside Rk3/Metformin-Loaded Hydrogel Microneedle for Management of Systemic Sclerosis |
| title_sort | self adhesive ginsenoside rk3 metformin loaded hydrogel microneedle for management of systemic sclerosis |
| topic | systemic sclerosis hydrogel microneedle CXCL4/TGF-β ultra-long release reverse skin phenotype |
| url | https://www.mdpi.com/2310-2861/11/6/384 |
| work_keys_str_mv | AT yuanyuanwang aselfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT caiyunzhong aselfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT kexinwang aselfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT shihongshen aselfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT daidifan aselfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT yuanyuanwang selfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT caiyunzhong selfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT kexinwang selfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT shihongshen selfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis AT daidifan selfadhesiveginsenosiderk3metforminloadedhydrogelmicroneedleformanagementofsystemicsclerosis |