Thioctamer: a novel thioctic acid-glatiramer acetate nanoconjugate expedites wound healing in diabetic rats
The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer preclinical efficacy in expediting wound healing in a rat model of the diabetic wound. Thioctamer was prepared by conjugation of GA an...
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| creator | Alhakamy, Nabil A. Mohamed, Gamal A. Fahmy, Usama A. Eid, Basma G. Al-Rabia, Mohammed W. Khedr, Amgad I. M. Nasrullah, Mohammed Z. Ibrahim, Sabrin R. M. Abdel-Naim, Ashraf B. Ahmed, Osama A. A. Md, Shadab |
| description | The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer preclinical efficacy in expediting wound healing in a rat model of the diabetic wound. Thioctamer was prepared by conjugation of GA and TA in a 1:1 molar ratio. Particle size, zeta potential, and thermodynamic stability of the prepared thioctamer were assessed. Thioctamer was loaded in hydroxypropyl methylcellulose-based hydrogel and in vitro release study was investigated. The ability of thioctamer to enhance the process of wound healing in diabetic rats was investigated by assessing wound contraction and immunohistochemical assessment of the inflammation markers IL-6 and TNF-α. The results demonstrated that thioctamer showed particle size of 137 ± 21.4 nm, polydispersity index (PDI) of 0.235, and positive zeta potential value of 7.43 ± 4.95 mV. On day 10 of making a skin excision, diabetic rat wounds administered thioctamer preparation showed almost complete healing (95.6 ± 8.6%). Meanwhile, % of wound contraction in animals treated with TA or GA groups exhibited values amounting to 56.5 ± 5.8% and 62.6 ± 7.1%, respectively. Histological investigation showed that the highest healing rate was noted in the thioctamer group animals, as the surface of the wound was nearly fully protected by regenerated epithelium with keratinization, with few inflammatory cells noticed. Thioctamer significantly (p |
| doi_str_mv | 10.1080/10717544.2022.2081382 |
| format | Article |
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M. ; Nasrullah, Mohammed Z. ; Ibrahim, Sabrin R. M. ; Abdel-Naim, Ashraf B. ; Ahmed, Osama A. A. ; Md, Shadab</creator><creatorcontrib>Alhakamy, Nabil A. ; Mohamed, Gamal A. ; Fahmy, Usama A. ; Eid, Basma G. ; Al-Rabia, Mohammed W. ; Khedr, Amgad I. M. ; Nasrullah, Mohammed Z. ; Ibrahim, Sabrin R. M. ; Abdel-Naim, Ashraf B. ; Ahmed, Osama A. A. ; Md, Shadab</creatorcontrib><description>The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer preclinical efficacy in expediting wound healing in a rat model of the diabetic wound. Thioctamer was prepared by conjugation of GA and TA in a 1:1 molar ratio. Particle size, zeta potential, and thermodynamic stability of the prepared thioctamer were assessed. Thioctamer was loaded in hydroxypropyl methylcellulose-based hydrogel and in vitro release study was investigated. The ability of thioctamer to enhance the process of wound healing in diabetic rats was investigated by assessing wound contraction and immunohistochemical assessment of the inflammation markers IL-6 and TNF-α. The results demonstrated that thioctamer showed particle size of 137 ± 21.4 nm, polydispersity index (PDI) of 0.235, and positive zeta potential value of 7.43 ± 4.95 mV. On day 10 of making a skin excision, diabetic rat wounds administered thioctamer preparation showed almost complete healing (95.6 ± 8.6%). Meanwhile, % of wound contraction in animals treated with TA or GA groups exhibited values amounting to 56.5 ± 5.8% and 62.6 ± 7.1%, respectively. Histological investigation showed that the highest healing rate was noted in the thioctamer group animals, as the surface of the wound was nearly fully protected by regenerated epithelium with keratinization, with few inflammatory cells noticed. Thioctamer significantly (p<.05) inhibited IL-6 and TNF-α expression as compared with sections obtained from the negative control, TA, GA, or positive control group animals on day 14. The evidence of the ability of thioctamer to significantly expedite wound healing in the diabetic rats is presented.</description><identifier>ISSN: 1071-7544</identifier><identifier>EISSN: 1521-0464</identifier><identifier>DOI: 10.1080/10717544.2022.2081382</identifier><identifier>PMID: 35642489</identifier><language>eng</language><publisher>England: Taylor & Francis</publisher><subject>Alpha-lipoic acid ; Animals ; Diabetes ; Diabetes Mellitus, Experimental - drug therapy ; Diabetes Mellitus, Experimental - pathology ; diabetic wounds ; Glatiramer Acetate ; HPMC hydrogel ; Hydrogels ; IL-6 ; Interleukin-6 ; Investigations ; Nanoconjugates ; nanoparticles ; Particle size ; Rats ; Thioctic Acid ; TNF-α ; Tumor Necrosis Factor-alpha ; Wound Healing</subject><ispartof>Drug delivery, 2022-12, Vol.29 (1), p.1776-1784</ispartof><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. This work is licensed under the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2022 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group. 2022 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4772-2d3b4ae62be2afa88ac886bc84763b80f7cf66b566ad2b6d4f45058c0c7f30c53</citedby><cites>FETCH-LOGICAL-c4772-2d3b4ae62be2afa88ac886bc84763b80f7cf66b566ad2b6d4f45058c0c7f30c53</cites><orcidid>0000-0002-3826-1519 ; 0000-0002-9343-1066</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176700/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC9176700/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,27481,27903,27904,53769,53771,59119,59120</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35642489$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Alhakamy, Nabil A.</creatorcontrib><creatorcontrib>Mohamed, Gamal A.</creatorcontrib><creatorcontrib>Fahmy, Usama A.</creatorcontrib><creatorcontrib>Eid, Basma G.</creatorcontrib><creatorcontrib>Al-Rabia, Mohammed W.</creatorcontrib><creatorcontrib>Khedr, Amgad I. M.</creatorcontrib><creatorcontrib>Nasrullah, Mohammed Z.</creatorcontrib><creatorcontrib>Ibrahim, Sabrin R. M.</creatorcontrib><creatorcontrib>Abdel-Naim, Ashraf B.</creatorcontrib><creatorcontrib>Ahmed, Osama A. A.</creatorcontrib><creatorcontrib>Md, Shadab</creatorcontrib><title>Thioctamer: a novel thioctic acid-glatiramer acetate nanoconjugate expedites wound healing in diabetic rats</title><title>Drug delivery</title><addtitle>Drug Deliv</addtitle><description>The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer preclinical efficacy in expediting wound healing in a rat model of the diabetic wound. Thioctamer was prepared by conjugation of GA and TA in a 1:1 molar ratio. Particle size, zeta potential, and thermodynamic stability of the prepared thioctamer were assessed. Thioctamer was loaded in hydroxypropyl methylcellulose-based hydrogel and in vitro release study was investigated. The ability of thioctamer to enhance the process of wound healing in diabetic rats was investigated by assessing wound contraction and immunohistochemical assessment of the inflammation markers IL-6 and TNF-α. The results demonstrated that thioctamer showed particle size of 137 ± 21.4 nm, polydispersity index (PDI) of 0.235, and positive zeta potential value of 7.43 ± 4.95 mV. On day 10 of making a skin excision, diabetic rat wounds administered thioctamer preparation showed almost complete healing (95.6 ± 8.6%). Meanwhile, % of wound contraction in animals treated with TA or GA groups exhibited values amounting to 56.5 ± 5.8% and 62.6 ± 7.1%, respectively. Histological investigation showed that the highest healing rate was noted in the thioctamer group animals, as the surface of the wound was nearly fully protected by regenerated epithelium with keratinization, with few inflammatory cells noticed. Thioctamer significantly (p<.05) inhibited IL-6 and TNF-α expression as compared with sections obtained from the negative control, TA, GA, or positive control group animals on day 14. The evidence of the ability of thioctamer to significantly expedite wound healing in the diabetic rats is presented.</description><subject>Alpha-lipoic acid</subject><subject>Animals</subject><subject>Diabetes</subject><subject>Diabetes Mellitus, Experimental - drug therapy</subject><subject>Diabetes Mellitus, Experimental - pathology</subject><subject>diabetic wounds</subject><subject>Glatiramer Acetate</subject><subject>HPMC hydrogel</subject><subject>Hydrogels</subject><subject>IL-6</subject><subject>Interleukin-6</subject><subject>Investigations</subject><subject>Nanoconjugates</subject><subject>nanoparticles</subject><subject>Particle size</subject><subject>Rats</subject><subject>Thioctic Acid</subject><subject>TNF-α</subject><subject>Tumor Necrosis Factor-alpha</subject><subject>Wound Healing</subject><issn>1071-7544</issn><issn>1521-0464</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>0YH</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNp9kstu1TAQhiMEoqXwCKBIbNik2I5vYYGKKi6VKrEpa2viS44PiX2wk5a-PU7PaUVZsLE9429-j-2_ql5jdIqRRO8xElgwSk8JIqQMEreSPKmOMSO4QZTTp2VdmGaFjqoXOW8RKhRhz6ujlnFKqOyOq59XGx_1DJNNH2qoQ7y2Yz3f5byuQXvTDCPMPq1Eie0Ms60DhKhj2C7DGtnfO2v8bHN9E5dg6o2F0Yeh9qE2Hnq7KiWY88vqmYMx21eH-aT68eXz1fm35vL714vzT5eNpkKQhpi2p2A56S0BB1KClpL3WlLB214iJ7TjvGecgyE9N9RRhpjUSAvXIs3ak-pir2sibNUu-QnSrYrg1V0ipkFBKk2NVnFNWqMNdlQTSgFLKiVhTqKOdFowXrQ-7rV2Sz9Zo22YE4yPRB_vBL9RQ7xWHRZcIFQE3h0EUvy12DyryWdtxxGCjUtWhAvSEsQpLejbf9BtXFIoT6VI-cWu46WvQrE9pVPMOVn30AxGarWGureGWq2hDtYodW_-vslD1b0XCnC2B3xwMU1wE9No1Ay3Y0wuQdA-q_b_Z_wBxfXJWQ</recordid><startdate>202212</startdate><enddate>202212</enddate><creator>Alhakamy, Nabil A.</creator><creator>Mohamed, Gamal A.</creator><creator>Fahmy, Usama A.</creator><creator>Eid, Basma G.</creator><creator>Al-Rabia, Mohammed W.</creator><creator>Khedr, Amgad I. 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A.</creator><creator>Md, Shadab</creator><general>Taylor & Francis</general><general>Taylor & Francis Ltd</general><general>Taylor & Francis Group</general><scope>0YH</scope><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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88I</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>COVID</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M2P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope><orcidid>https://orcid.org/0000-0002-3826-1519</orcidid><orcidid>https://orcid.org/0000-0002-9343-1066</orcidid></search><sort><creationdate>202212</creationdate><title>Thioctamer: a novel thioctic acid-glatiramer acetate nanoconjugate expedites wound healing in diabetic rats</title><author>Alhakamy, Nabil A. ; Mohamed, Gamal A. ; Fahmy, Usama A. ; Eid, Basma G. ; Al-Rabia, Mohammed W. ; Khedr, Amgad I. M. ; Nasrullah, Mohammed Z. ; Ibrahim, Sabrin R. M. ; Abdel-Naim, Ashraf B. ; Ahmed, Osama A. A. ; Md, Shadab</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4772-2d3b4ae62be2afa88ac886bc84763b80f7cf66b566ad2b6d4f45058c0c7f30c53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Alpha-lipoic acid</topic><topic>Animals</topic><topic>Diabetes</topic><topic>Diabetes Mellitus, Experimental - drug therapy</topic><topic>Diabetes Mellitus, Experimental - pathology</topic><topic>diabetic wounds</topic><topic>Glatiramer Acetate</topic><topic>HPMC hydrogel</topic><topic>Hydrogels</topic><topic>IL-6</topic><topic>Interleukin-6</topic><topic>Investigations</topic><topic>Nanoconjugates</topic><topic>nanoparticles</topic><topic>Particle size</topic><topic>Rats</topic><topic>Thioctic Acid</topic><topic>TNF-α</topic><topic>Tumor Necrosis Factor-alpha</topic><topic>Wound Healing</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alhakamy, Nabil A.</creatorcontrib><creatorcontrib>Mohamed, Gamal A.</creatorcontrib><creatorcontrib>Fahmy, Usama A.</creatorcontrib><creatorcontrib>Eid, Basma G.</creatorcontrib><creatorcontrib>Al-Rabia, Mohammed W.</creatorcontrib><creatorcontrib>Khedr, Amgad I. 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A.</creatorcontrib><creatorcontrib>Md, Shadab</creatorcontrib><collection>Taylor & Francis Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Science Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Coronavirus Research Database</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>Drug delivery</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alhakamy, Nabil A.</au><au>Mohamed, Gamal A.</au><au>Fahmy, Usama A.</au><au>Eid, Basma G.</au><au>Al-Rabia, Mohammed W.</au><au>Khedr, Amgad I. M.</au><au>Nasrullah, Mohammed Z.</au><au>Ibrahim, Sabrin R. M.</au><au>Abdel-Naim, Ashraf B.</au><au>Ahmed, Osama A. A.</au><au>Md, Shadab</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Thioctamer: a novel thioctic acid-glatiramer acetate nanoconjugate expedites wound healing in diabetic rats</atitle><jtitle>Drug delivery</jtitle><addtitle>Drug Deliv</addtitle><date>2022-12</date><risdate>2022</risdate><volume>29</volume><issue>1</issue><spage>1776</spage><epage>1784</epage><pages>1776-1784</pages><issn>1071-7544</issn><eissn>1521-0464</eissn><abstract>The current work aims to design thioctic acid (TA) and glatiramer acetate (GA) nanoconjugate (thioctamer) loaded hydrogel formula as well as evaluation of thioctamer preclinical efficacy in expediting wound healing in a rat model of the diabetic wound. Thioctamer was prepared by conjugation of GA and TA in a 1:1 molar ratio. Particle size, zeta potential, and thermodynamic stability of the prepared thioctamer were assessed. Thioctamer was loaded in hydroxypropyl methylcellulose-based hydrogel and in vitro release study was investigated. The ability of thioctamer to enhance the process of wound healing in diabetic rats was investigated by assessing wound contraction and immunohistochemical assessment of the inflammation markers IL-6 and TNF-α. The results demonstrated that thioctamer showed particle size of 137 ± 21.4 nm, polydispersity index (PDI) of 0.235, and positive zeta potential value of 7.43 ± 4.95 mV. On day 10 of making a skin excision, diabetic rat wounds administered thioctamer preparation showed almost complete healing (95.6 ± 8.6%). Meanwhile, % of wound contraction in animals treated with TA or GA groups exhibited values amounting to 56.5 ± 5.8% and 62.6 ± 7.1%, respectively. Histological investigation showed that the highest healing rate was noted in the thioctamer group animals, as the surface of the wound was nearly fully protected by regenerated epithelium with keratinization, with few inflammatory cells noticed. Thioctamer significantly (p<.05) inhibited IL-6 and TNF-α expression as compared with sections obtained from the negative control, TA, GA, or positive control group animals on day 14. The evidence of the ability of thioctamer to significantly expedite wound healing in the diabetic rats is presented.</abstract><cop>England</cop><pub>Taylor & Francis</pub><pmid>35642489</pmid><doi>10.1080/10717544.2022.2081382</doi><tpages>9</tpages><orcidid>https://orcid.org/0000-0002-3826-1519</orcidid><orcidid>https://orcid.org/0000-0002-9343-1066</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Taylor & Francis Open Access; MEDLINE; DOAJ Directory of Open Access Journals; EZB-FREE-00999 freely available EZB journals; PubMed Central; Alma/SFX Local Collection |
| subjects | Alpha-lipoic acid Animals Diabetes Diabetes Mellitus, Experimental - drug therapy Diabetes Mellitus, Experimental - pathology diabetic wounds Glatiramer Acetate HPMC hydrogel Hydrogels IL-6 Interleukin-6 Investigations Nanoconjugates nanoparticles Particle size Rats Thioctic Acid TNF-α Tumor Necrosis Factor-alpha Wound Healing |
| title | Thioctamer: a novel thioctic acid-glatiramer acetate nanoconjugate expedites wound healing in diabetic rats |
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