A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing
Treating infected wounds is facing a serious challenge due to the rapid spread of antibiotic resistance worldwide. In the search for novel antimicrobial drugs, natural products often serve as a crucial resource. Plumbagin (PLB) is the most important natural active ingredient in the root of Plumbago...
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| Veröffentlicht in: | Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2025-02, Vol.246, p.114377, Article 114377 |
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| creator | Lu, Xuemei Zhang, Jingqing Zuo, Wanyu Cheng, Bingyu Dong, Ruyin Wang, Weiyu Lu, Luyang |
| description | Treating infected wounds is facing a serious challenge due to the rapid spread of antibiotic resistance worldwide. In the search for novel antimicrobial drugs, natural products often serve as a crucial resource. Plumbagin (PLB) is the most important natural active ingredient in the root of Plumbago zeylanica L. known for its excellent antibacterial ability. However, the application of PLB is limited because of its poor water solubility, instability, and tendency to sublimate. In this study, we propose a solution by designing a hyaluronic acid (HA)/polyvinylpyrrolidone (PVP) dissolving microneedle patch loaded with PLB/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex. PLB was encapsulated into the cavity of HP-β-CD to improve its solubility and stability using the neutralization agitation method. The formation of the inclusion complex significantly increased the water solubility of PLB to 1350 ± 6.8 μg/mL, which is 17 times higher than its original value of 79.3 ± 1.7 μg/mL. The encapsulation efficiency was found to be 94.82 ± 3.34 %. In vitro drug release studies, PLB microneedles loaded with PLB/HP-β-CD inclusion complex rapidly released into PBS within 15 min. Furthermore, the PLB microneedles exhibited strong antibacterial activity against Staphylococcus aureus (S. aureus) both in vivo and in vitro. They also remarkably accelerated the healing of infected wounds in mice by enhancing collagen deposition and re-epithelialization, reducing inflammation, and stimulating angiogenesis. Overall, this multifunctional microneedle patch shows promising potential for clinical applications in the healing of infected wounds.
•Transdermal microneedle patch loaded with plumbagin inclusion complex was developed.•Plumbagin/hydroxypropyl-β-cyclodextrin complex showed high encapsulation efficiency.•Solved the shortcomings of poor water solubility, instability, and easy sublimation.•In vitro and in vivo results indicated potential value for infected wound healing. |
| doi_str_mv | 10.1016/j.colsurfb.2024.114377 |
| format | Article |
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•Transdermal microneedle patch loaded with plumbagin inclusion complex was developed.•Plumbagin/hydroxypropyl-β-cyclodextrin complex showed high encapsulation efficiency.•Solved the shortcomings of poor water solubility, instability, and easy sublimation.•In vitro and in vivo results indicated potential value for infected wound healing.</description><identifier>ISSN: 0927-7765</identifier><identifier>ISSN: 1873-4367</identifier><identifier>EISSN: 1873-4367</identifier><identifier>DOI: 10.1016/j.colsurfb.2024.114377</identifier><identifier>PMID: 39577147</identifier><language>eng</language><publisher>Netherlands: Elsevier B.V</publisher><subject>2-Hydroxypropyl-beta-cyclodextrin - chemistry ; active ingredients ; agitation ; angiogenesis ; Animals ; Anti-Bacterial Agents - administration & dosage ; Anti-Bacterial Agents - chemistry ; Anti-Bacterial Agents - pharmacology ; Antibacterial activity ; antibacterial properties ; antibiotic resistance ; collagen ; Dissolving microneedle ; Drug Liberation ; drugs ; encapsulation ; hyaluronic acid ; Hyaluronic Acid - chemistry ; Inclusion complex ; Infected wound healing ; inflammation ; Male ; Mice ; Microbial Sensitivity Tests ; Naphthoquinones - administration & dosage ; Naphthoquinones - chemistry ; Naphthoquinones - pharmacology ; Needles ; neutralization ; Plumbagin ; Plumbago zeylanica ; Solubility ; Staphylococcus aureus ; Staphylococcus aureus - drug effects ; Transdermal Patch ; water solubility ; Wound Healing - drug effects</subject><ispartof>Colloids and surfaces, B, Biointerfaces, 2025-02, Vol.246, p.114377, Article 114377</ispartof><rights>2024</rights><rights>Copyright © 2024. Published by Elsevier B.V.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c278t-5dd8e9f22303d415fa33d6b18d20b21623de44d6f85ad391fc669fdbb1643fd63</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0927776524006362$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39577147$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lu, Xuemei</creatorcontrib><creatorcontrib>Zhang, Jingqing</creatorcontrib><creatorcontrib>Zuo, Wanyu</creatorcontrib><creatorcontrib>Cheng, Bingyu</creatorcontrib><creatorcontrib>Dong, Ruyin</creatorcontrib><creatorcontrib>Wang, Weiyu</creatorcontrib><creatorcontrib>Lu, Luyang</creatorcontrib><title>A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing</title><title>Colloids and surfaces, B, Biointerfaces</title><addtitle>Colloids Surf B Biointerfaces</addtitle><description>Treating infected wounds is facing a serious challenge due to the rapid spread of antibiotic resistance worldwide. In the search for novel antimicrobial drugs, natural products often serve as a crucial resource. Plumbagin (PLB) is the most important natural active ingredient in the root of Plumbago zeylanica L. known for its excellent antibacterial ability. However, the application of PLB is limited because of its poor water solubility, instability, and tendency to sublimate. In this study, we propose a solution by designing a hyaluronic acid (HA)/polyvinylpyrrolidone (PVP) dissolving microneedle patch loaded with PLB/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex. PLB was encapsulated into the cavity of HP-β-CD to improve its solubility and stability using the neutralization agitation method. The formation of the inclusion complex significantly increased the water solubility of PLB to 1350 ± 6.8 μg/mL, which is 17 times higher than its original value of 79.3 ± 1.7 μg/mL. The encapsulation efficiency was found to be 94.82 ± 3.34 %. In vitro drug release studies, PLB microneedles loaded with PLB/HP-β-CD inclusion complex rapidly released into PBS within 15 min. Furthermore, the PLB microneedles exhibited strong antibacterial activity against Staphylococcus aureus (S. aureus) both in vivo and in vitro. They also remarkably accelerated the healing of infected wounds in mice by enhancing collagen deposition and re-epithelialization, reducing inflammation, and stimulating angiogenesis. Overall, this multifunctional microneedle patch shows promising potential for clinical applications in the healing of infected wounds.
•Transdermal microneedle patch loaded with plumbagin inclusion complex was developed.•Plumbagin/hydroxypropyl-β-cyclodextrin complex showed high encapsulation efficiency.•Solved the shortcomings of poor water solubility, instability, and easy sublimation.•In vitro and in vivo results indicated potential value for infected wound healing.</description><subject>2-Hydroxypropyl-beta-cyclodextrin - chemistry</subject><subject>active ingredients</subject><subject>agitation</subject><subject>angiogenesis</subject><subject>Animals</subject><subject>Anti-Bacterial Agents - administration & dosage</subject><subject>Anti-Bacterial Agents - chemistry</subject><subject>Anti-Bacterial Agents - pharmacology</subject><subject>Antibacterial activity</subject><subject>antibacterial properties</subject><subject>antibiotic resistance</subject><subject>collagen</subject><subject>Dissolving microneedle</subject><subject>Drug Liberation</subject><subject>drugs</subject><subject>encapsulation</subject><subject>hyaluronic acid</subject><subject>Hyaluronic Acid - chemistry</subject><subject>Inclusion complex</subject><subject>Infected wound healing</subject><subject>inflammation</subject><subject>Male</subject><subject>Mice</subject><subject>Microbial Sensitivity Tests</subject><subject>Naphthoquinones - administration & dosage</subject><subject>Naphthoquinones - chemistry</subject><subject>Naphthoquinones - pharmacology</subject><subject>Needles</subject><subject>neutralization</subject><subject>Plumbagin</subject><subject>Plumbago zeylanica</subject><subject>Solubility</subject><subject>Staphylococcus aureus</subject><subject>Staphylococcus aureus - drug effects</subject><subject>Transdermal Patch</subject><subject>water solubility</subject><subject>Wound Healing - drug effects</subject><issn>0927-7765</issn><issn>1873-4367</issn><issn>1873-4367</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2025</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqNkc1u3CAURlHVKpmmeYWIZTeeGLDB3jWK-idF6qZdI5t7yTDCxgU7Ha_6TnmQPFMZTdJtu0JC597v6juEXLFyy0omr_dbE3xaou23vOTVlrFKKPWKbFijRFEJqV6TTdlyVSgl63PyNqV9WWaSqTNyLtpaKVapDfl9Q8GlFPyDG-_p4EwMIyJ4pFM3mx31oQME-svNOzr5Zei7ezde71aI4bBOMUyrL54eC7MaHwAPc3QjdaPxS3JhpCYMk8cDtSHmX4tmPu4Kywh0h53Pke_IG9v5hJfP7wX58enj99svxd23z19vb-4Kw1UzFzVAg63lXJQCKlbbTgiQPWuAlz1nkgvAqgJpm7oD0TJrpGwt9D2TlbAgxQV5f9qbb_65YJr14JJB77sRw5K0YHXFZc1r8R-o4CzfUPOMyhOaa0spotVTdEMXV81KffSk9_rFkz560idPefDqOWPpB4S_Yy9iMvDhBGAu5cFh1Mk4HA2Ci7lGDcH9K-MPk8Crhw</recordid><startdate>20250201</startdate><enddate>20250201</enddate><creator>Lu, Xuemei</creator><creator>Zhang, Jingqing</creator><creator>Zuo, Wanyu</creator><creator>Cheng, Bingyu</creator><creator>Dong, Ruyin</creator><creator>Wang, Weiyu</creator><creator>Lu, Luyang</creator><general>Elsevier B.V</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>7S9</scope><scope>L.6</scope></search><sort><creationdate>20250201</creationdate><title>A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing</title><author>Lu, Xuemei ; Zhang, Jingqing ; Zuo, Wanyu ; Cheng, Bingyu ; Dong, Ruyin ; Wang, Weiyu ; Lu, Luyang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c278t-5dd8e9f22303d415fa33d6b18d20b21623de44d6f85ad391fc669fdbb1643fd63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2025</creationdate><topic>2-Hydroxypropyl-beta-cyclodextrin - chemistry</topic><topic>active ingredients</topic><topic>agitation</topic><topic>angiogenesis</topic><topic>Animals</topic><topic>Anti-Bacterial Agents - administration & dosage</topic><topic>Anti-Bacterial Agents - chemistry</topic><topic>Anti-Bacterial Agents - pharmacology</topic><topic>Antibacterial activity</topic><topic>antibacterial properties</topic><topic>antibiotic resistance</topic><topic>collagen</topic><topic>Dissolving microneedle</topic><topic>Drug Liberation</topic><topic>drugs</topic><topic>encapsulation</topic><topic>hyaluronic acid</topic><topic>Hyaluronic Acid - chemistry</topic><topic>Inclusion complex</topic><topic>Infected wound healing</topic><topic>inflammation</topic><topic>Male</topic><topic>Mice</topic><topic>Microbial Sensitivity Tests</topic><topic>Naphthoquinones - administration & dosage</topic><topic>Naphthoquinones - chemistry</topic><topic>Naphthoquinones - pharmacology</topic><topic>Needles</topic><topic>neutralization</topic><topic>Plumbagin</topic><topic>Plumbago zeylanica</topic><topic>Solubility</topic><topic>Staphylococcus aureus</topic><topic>Staphylococcus aureus - drug effects</topic><topic>Transdermal Patch</topic><topic>water solubility</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lu, Xuemei</creatorcontrib><creatorcontrib>Zhang, Jingqing</creatorcontrib><creatorcontrib>Zuo, Wanyu</creatorcontrib><creatorcontrib>Cheng, Bingyu</creatorcontrib><creatorcontrib>Dong, Ruyin</creatorcontrib><creatorcontrib>Wang, Weiyu</creatorcontrib><creatorcontrib>Lu, Luyang</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>AGRICOLA</collection><collection>AGRICOLA - Academic</collection><jtitle>Colloids and surfaces, B, Biointerfaces</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lu, Xuemei</au><au>Zhang, Jingqing</au><au>Zuo, Wanyu</au><au>Cheng, Bingyu</au><au>Dong, Ruyin</au><au>Wang, Weiyu</au><au>Lu, Luyang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing</atitle><jtitle>Colloids and surfaces, B, Biointerfaces</jtitle><addtitle>Colloids Surf B Biointerfaces</addtitle><date>2025-02-01</date><risdate>2025</risdate><volume>246</volume><spage>114377</spage><pages>114377-</pages><artnum>114377</artnum><issn>0927-7765</issn><issn>1873-4367</issn><eissn>1873-4367</eissn><abstract>Treating infected wounds is facing a serious challenge due to the rapid spread of antibiotic resistance worldwide. In the search for novel antimicrobial drugs, natural products often serve as a crucial resource. Plumbagin (PLB) is the most important natural active ingredient in the root of Plumbago zeylanica L. known for its excellent antibacterial ability. However, the application of PLB is limited because of its poor water solubility, instability, and tendency to sublimate. In this study, we propose a solution by designing a hyaluronic acid (HA)/polyvinylpyrrolidone (PVP) dissolving microneedle patch loaded with PLB/hydroxypropyl-β-cyclodextrin (HP-β-CD) inclusion complex. PLB was encapsulated into the cavity of HP-β-CD to improve its solubility and stability using the neutralization agitation method. The formation of the inclusion complex significantly increased the water solubility of PLB to 1350 ± 6.8 μg/mL, which is 17 times higher than its original value of 79.3 ± 1.7 μg/mL. The encapsulation efficiency was found to be 94.82 ± 3.34 %. In vitro drug release studies, PLB microneedles loaded with PLB/HP-β-CD inclusion complex rapidly released into PBS within 15 min. Furthermore, the PLB microneedles exhibited strong antibacterial activity against Staphylococcus aureus (S. aureus) both in vivo and in vitro. They also remarkably accelerated the healing of infected wounds in mice by enhancing collagen deposition and re-epithelialization, reducing inflammation, and stimulating angiogenesis. Overall, this multifunctional microneedle patch shows promising potential for clinical applications in the healing of infected wounds.
•Transdermal microneedle patch loaded with plumbagin inclusion complex was developed.•Plumbagin/hydroxypropyl-β-cyclodextrin complex showed high encapsulation efficiency.•Solved the shortcomings of poor water solubility, instability, and easy sublimation.•In vitro and in vivo results indicated potential value for infected wound healing.</abstract><cop>Netherlands</cop><pub>Elsevier B.V</pub><pmid>39577147</pmid><doi>10.1016/j.colsurfb.2024.114377</doi></addata></record> |
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| subjects | 2-Hydroxypropyl-beta-cyclodextrin - chemistry active ingredients agitation angiogenesis Animals Anti-Bacterial Agents - administration & dosage Anti-Bacterial Agents - chemistry Anti-Bacterial Agents - pharmacology Antibacterial activity antibacterial properties antibiotic resistance collagen Dissolving microneedle Drug Liberation drugs encapsulation hyaluronic acid Hyaluronic Acid - chemistry Inclusion complex Infected wound healing inflammation Male Mice Microbial Sensitivity Tests Naphthoquinones - administration & dosage Naphthoquinones - chemistry Naphthoquinones - pharmacology Needles neutralization Plumbagin Plumbago zeylanica Solubility Staphylococcus aureus Staphylococcus aureus - drug effects Transdermal Patch water solubility Wound Healing - drug effects |
| title | A dissolving microneedle patch loaded with plumbagin/hydroxypropyl-β-cyclodextrin inclusion complex for infected wound healing |
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