{"title":"一种由丝绸蛋白启发的强力组织粘合剂,具有增强的药物释放机制,可用于透皮给药。","authors":"Haoyuan Song, Liuyang Wang, Jiaxu Wu, Jie Liu, Chao Liu, Jianpeng Guo, Liang Fang","doi":"10.1016/j.actbio.2024.04.024","DOIUrl":null,"url":null,"abstract":"<div><p>In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu<sup>2+</sup> adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu<sup>2+</sup> to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu<sup>2+</sup>-p-π conjugated network in PHT-SP-Cu<sup>2+</sup> were characterized and elucidated using different characterization methods including FT-IR, <sup>13</sup>C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu<sup>2+</sup> provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu<sup>2+</sup> was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87–4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu<sup>2+</sup> could adhere to the human body for more than six days. Moreover, the drug loading, <em>in vitro</em> release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu<sup>2+</sup> had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu<sup>2+</sup> was increased by 6.25-fold compared with PHT, and in the <em>in vivo</em> pharmacokinetic analysis, the <em>AUC</em> was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu<sup>2+</sup> for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency.</p></div><div><h3>Statement of significance</h3><p>A new adhesive, PHT-SP-Cu<sup>2+</sup>, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu<sup>2+</sup> were used in synthesis. Characterization techniques confirmed the structure and Cu<sup>2+</sup>-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu<sup>2+</sup>, exhibiting superior adhesion. PHT-SP-Cu<sup>2+</sup> showed 7.6 times higher peel strength than DURO-TAK® 87–4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher <em>AUC in vivo</em> studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu<sup>2+</sup> showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches.</p></div>","PeriodicalId":237,"journal":{"name":"Acta Biomaterialia","volume":null,"pages":null},"PeriodicalIF":9.4000,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"A strong, silk protein-inspired tissue adhesive with an enhanced drug release mechanism for transdermal drug delivery\",\"authors\":\"Haoyuan Song, Liuyang Wang, Jiaxu Wu, Jie Liu, Chao Liu, Jianpeng Guo, Liang Fang\",\"doi\":\"10.1016/j.actbio.2024.04.024\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu<sup>2+</sup> adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu<sup>2+</sup> to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu<sup>2+</sup>-p-π conjugated network in PHT-SP-Cu<sup>2+</sup> were characterized and elucidated using different characterization methods including FT-IR, <sup>13</sup>C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu<sup>2+</sup> provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu<sup>2+</sup> was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87–4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu<sup>2+</sup> could adhere to the human body for more than six days. Moreover, the drug loading, <em>in vitro</em> release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu<sup>2+</sup> had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu<sup>2+</sup> was increased by 6.25-fold compared with PHT, and in the <em>in vivo</em> pharmacokinetic analysis, the <em>AUC</em> was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu<sup>2+</sup> for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency.</p></div><div><h3>Statement of significance</h3><p>A new adhesive, PHT-SP-Cu<sup>2+</sup>, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu<sup>2+</sup> were used in synthesis. Characterization techniques confirmed the structure and Cu<sup>2+</sup>-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu<sup>2+</sup>, exhibiting superior adhesion. PHT-SP-Cu<sup>2+</sup> showed 7.6 times higher peel strength than DURO-TAK® 87–4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher <em>AUC in vivo</em> studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu<sup>2+</sup> showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches.</p></div>\",\"PeriodicalId\":237,\"journal\":{\"name\":\"Acta Biomaterialia\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":9.4000,\"publicationDate\":\"2024-06-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Acta Biomaterialia\",\"FirstCategoryId\":\"5\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S1742706124001971\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENGINEERING, BIOMEDICAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Biomaterialia","FirstCategoryId":"5","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S1742706124001971","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENGINEERING, BIOMEDICAL","Score":null,"Total":0}
A strong, silk protein-inspired tissue adhesive with an enhanced drug release mechanism for transdermal drug delivery
In transdermal drug delivery system (TDDS) patches, achieving prolonged adhesion, high drug loading, and rapid drug release simultaneously presented a significant challenge. In this study, a PHT-SP-Cu2+ adhesive was synthesized using polyethylene glycol (PEG), hexamethylene diisocyanate (HDI), trimethylolpropane (TMP), and silk protein (SP) as functional monomers which were combined with Cu2+ to improve the adhesion, drug loading, and drug release of the patch. The structure of the adhesion chains and the formation of Cu2+-p-π conjugated network in PHT-SP-Cu2+ were characterized and elucidated using different characterization methods including FT-IR, 13C NMR, XPS, SEM imaging and thermodynamic evaluation. The formulation of pressure-sensitive adhesive (PSA) was optimized through comprehensive research on adhesion, mechanics, rheology, and surface energy. The formulation of 3 wt.% SP and 3 wt.% Cu2+ provided superior adhesion properties compared to commercial standards. Subsequently, the peel strength of PHT-SP-Cu2+ was 7.6 times higher than that of the commercially available adhesive DURO-TAK® 87–4098 in the porcine skin peel test. The adhesion test on human skin confirmed that PHT-SP-Cu2+ could adhere to the human body for more than six days. Moreover, the drug loading, in vitro release test and skin permeation test were investigated using ketoprofen as a model drug, and the results showed that PHT-SP-Cu2+ had the efficacy of improving drug compatibility, promoting drug release and enhancing skin permeation as a TDDS. Among them, the drug loading of PHT-SP-Cu2+ was increased by 6.25-fold compared with PHT, and in the in vivo pharmacokinetic analysis, the AUC was similarly increased by 19.22-fold. The mechanism of α-helix facilitated drug release was demonstrated by Flori-Hawkins interaction parameters, molecular dynamics simulations and FT-IR. Biosafety evaluations highlighted the superior skin cytocompatibility and safety of PHT-SP-Cu2+ for transdermal applications. These results would contribute to the development of TDDS patch adhesives with outstanding adhesion, drug loading and release efficiency.
Statement of significance
A new adhesive, PHT-SP-Cu2+, was created for transdermal drug delivery patches. Polyethylene glycol, hexamethylene diisocyanate, trimethylolpropane, silk protein, and Cu2+ were used in synthesis. Characterization techniques confirmed the structure and Cu2+-p-π conjugated networks. Optimal formulation included 3 wt.% SP and 3 wt.% Cu2+, exhibiting superior adhesion. PHT-SP-Cu2+ showed 7.6 times higher peel strength than DURO-TAK® 87–4098 on porcine skin and adhered to human skin for over six days. It demonstrated a 6.25-fold increase in drug loading compared to PHT, with 19.22-fold higher AUC in vivo studies. α-helix facilitated drug release, proven by various analyses. PHT-SP-Cu2+ showed excellent cytocompatibility and safety for transdermal applications. This study contributes to developing efficient TDDS patches.
期刊介绍:
Acta Biomaterialia is a monthly peer-reviewed scientific journal published by Elsevier. The journal was established in January 2005. The editor-in-chief is W.R. Wagner (University of Pittsburgh). The journal covers research in biomaterials science, including the interrelationship of biomaterial structure and function from macroscale to nanoscale. Topical coverage includes biomedical and biocompatible materials.