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Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes
D Tatovic 
,
M A McAteer,
J Barry,
A Barrientos,
K Rodríguez Terradillos,
I Perera,
E Kochba,
Y Levin,
M Dul,
S A Coulman,
J C Birchall,
C von Ruhland,
A Howell,
R Stenson,
M Alhadj Ali,
Steve Luzio ,
Gareth Dunseath ,
W Y Cheung,
Gail Holland ,
K May,
J R Ingram,
M M U Chowdhury,
F S Wong,
R Casas,
C Dayan,
J Ludvigsson,
Ivy Cheung
,
M A McAteer,
J Barry,
A Barrientos,
K Rodríguez Terradillos,
I Perera,
E Kochba,
Y Levin,
M Dul,
S A Coulman,
J C Birchall,
C von Ruhland,
A Howell,
R Stenson,
M Alhadj Ali,
Steve Luzio ,
Gareth Dunseath ,
W Y Cheung,
Gail Holland ,
K May,
J R Ingram,
M M U Chowdhury,
F S Wong,
R Casas,
C Dayan,
J Ludvigsson,
Ivy Cheung
Immunotherapy Advances, Volume: 2, Issue: 1
Swansea University Authors:
Steve Luzio , Gareth Dunseath , Gail Holland , Ivy Cheung
-
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© The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License
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DOI (Published version): 10.1093/immadv/ltac002
Abstract
Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human...
| Published in: | Immunotherapy Advances |
|---|---|
| ISSN: | 2732-4303 |
| Published: |
Oxford University Press (OUP)
2022
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| URI: | https://cronfa.swan.ac.uk/Record/cronfa61405 |
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<?xml version="1.0"?><rfc1807><datestamp>2022-10-28T17:04:25.8435381</datestamp><bib-version>v2</bib-version><id>61405</id><entry>2022-10-03</entry><title>Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes</title><swanseaauthors><author><sid>01491e1cd582746a654fad9addf0de16</sid><ORCID>0000-0002-7206-6530</ORCID><firstname>Steve</firstname><surname>Luzio</surname><name>Steve Luzio</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>fccbba9edcaee08a839a3c5cff8cbe19</sid><ORCID>0000-0001-6022-862X</ORCID><firstname>Gareth</firstname><surname>Dunseath</surname><name>Gareth Dunseath</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>b9f3a8bf7478db012c8856b7bbbc7597</sid><ORCID>0000-0002-6924-2521</ORCID><firstname>Gail</firstname><surname>Holland</surname><name>Gail Holland</name><active>true</active><ethesisStudent>false</ethesisStudent></author><author><sid>a9142ffd398f89eff40ada503e315639</sid><firstname>Ivy</firstname><surname>Cheung</surname><name>Ivy Cheung</name><active>true</active><ethesisStudent>false</ethesisStudent></author></swanseaauthors><date>2022-10-03</date><deptcode>BMS</deptcode><abstract>Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies.</abstract><type>Journal Article</type><journal>Immunotherapy Advances</journal><volume>2</volume><journalNumber>1</journalNumber><paginationStart/><paginationEnd/><publisher>Oxford University Press (OUP)</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint/><issnElectronic>2732-4303</issnElectronic><keywords>gold nanoparticle, peptide immunotherapy, microneedle, type 1 diabetes, proinsulin</keywords><publishedDay>18</publishedDay><publishedMonth>3</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-03-18</publishedDate><doi>10.1093/immadv/ltac002</doi><url/><notes/><college>COLLEGE NANME</college><department>Biomedical Sciences</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>BMS</DepartmentCode><institution>Swansea University</institution><apcterm>Another institution paid the OA fee</apcterm><funders>This work has been funded through the EE-ASI (The Enhanced
Epidermal Antigen Specific Immunotherapy Against Type
1 Diabetes) European research network (Collaborative
Project) supported by the European Commission under the
Health Cooperation Work Programme of the 7th Framework
Programme (grant no. N 305305).</funders><projectreference/><lastEdited>2022-10-28T17:04:25.8435381</lastEdited><Created>2022-10-03T14:34:04.0797356</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Medicine</level></path><authors><author><firstname>D</firstname><surname>Tatovic</surname><orcid>0000-0002-3879-2686</orcid><order>1</order></author><author><firstname>M A</firstname><surname>McAteer</surname><order>2</order></author><author><firstname>J</firstname><surname>Barry</surname><order>3</order></author><author><firstname>A</firstname><surname>Barrientos</surname><order>4</order></author><author><firstname>K Rodríguez</firstname><surname>Terradillos</surname><order>5</order></author><author><firstname>I</firstname><surname>Perera</surname><order>6</order></author><author><firstname>E</firstname><surname>Kochba</surname><order>7</order></author><author><firstname>Y</firstname><surname>Levin</surname><order>8</order></author><author><firstname>M</firstname><surname>Dul</surname><order>9</order></author><author><firstname>S A</firstname><surname>Coulman</surname><order>10</order></author><author><firstname>J C</firstname><surname>Birchall</surname><order>11</order></author><author><firstname>C von</firstname><surname>Ruhland</surname><order>12</order></author><author><firstname>A</firstname><surname>Howell</surname><order>13</order></author><author><firstname>R</firstname><surname>Stenson</surname><order>14</order></author><author><firstname>M Alhadj</firstname><surname>Ali</surname><order>15</order></author><author><firstname>Steve</firstname><surname>Luzio</surname><orcid>0000-0002-7206-6530</orcid><order>16</order></author><author><firstname>Gareth</firstname><surname>Dunseath</surname><orcid>0000-0001-6022-862X</orcid><order>17</order></author><author><firstname>W Y</firstname><surname>Cheung</surname><order>18</order></author><author><firstname>Gail</firstname><surname>Holland</surname><orcid>0000-0002-6924-2521</orcid><order>19</order></author><author><firstname>K</firstname><surname>May</surname><order>20</order></author><author><firstname>J R</firstname><surname>Ingram</surname><order>21</order></author><author><firstname>M M U</firstname><surname>Chowdhury</surname><order>22</order></author><author><firstname>F S</firstname><surname>Wong</surname><order>23</order></author><author><firstname>R</firstname><surname>Casas</surname><order>24</order></author><author><firstname>C</firstname><surname>Dayan</surname><order>25</order></author><author><firstname>J</firstname><surname>Ludvigsson</surname><order>26</order></author><author><firstname>Ivy</firstname><surname>Cheung</surname><order>27</order></author></authors><documents><document><filename>61405__25610__cdde90b78bb1451dbbd52f8428b7bb00.pdf</filename><originalFilename>61405_VoR.pdf</originalFilename><uploaded>2022-10-28T17:03:29.4923621</uploaded><type>Output</type><contentLength>14278267</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License</documentNotes><copyrightCorrect>true</copyrightCorrect><language>eng</language><licence>https://creativecommons.org/licenses/by-nc/4.0/</licence></document></documents><OutputDurs/></rfc1807> |
| spelling |
2022-10-28T17:04:25.8435381 v2 61405 2022-10-03 Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes 01491e1cd582746a654fad9addf0de16 0000-0002-7206-6530 Steve Luzio Steve Luzio true false fccbba9edcaee08a839a3c5cff8cbe19 0000-0001-6022-862X Gareth Dunseath Gareth Dunseath true false b9f3a8bf7478db012c8856b7bbbc7597 0000-0002-6924-2521 Gail Holland Gail Holland true false a9142ffd398f89eff40ada503e315639 Ivy Cheung Ivy Cheung true false 2022-10-03 BMS Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies. Journal Article Immunotherapy Advances 2 1 Oxford University Press (OUP) 2732-4303 gold nanoparticle, peptide immunotherapy, microneedle, type 1 diabetes, proinsulin 18 3 2022 2022-03-18 10.1093/immadv/ltac002 COLLEGE NANME Biomedical Sciences COLLEGE CODE BMS Swansea University Another institution paid the OA fee This work has been funded through the EE-ASI (The Enhanced Epidermal Antigen Specific Immunotherapy Against Type 1 Diabetes) European research network (Collaborative Project) supported by the European Commission under the Health Cooperation Work Programme of the 7th Framework Programme (grant no. N 305305). 2022-10-28T17:04:25.8435381 2022-10-03T14:34:04.0797356 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine D Tatovic 0000-0002-3879-2686 1 M A McAteer 2 J Barry 3 A Barrientos 4 K Rodríguez Terradillos 5 I Perera 6 E Kochba 7 Y Levin 8 M Dul 9 S A Coulman 10 J C Birchall 11 C von Ruhland 12 A Howell 13 R Stenson 14 M Alhadj Ali 15 Steve Luzio 0000-0002-7206-6530 16 Gareth Dunseath 0000-0001-6022-862X 17 W Y Cheung 18 Gail Holland 0000-0002-6924-2521 19 K May 20 J R Ingram 21 M M U Chowdhury 22 F S Wong 23 R Casas 24 C Dayan 25 J Ludvigsson 26 Ivy Cheung 27 61405__25610__cdde90b78bb1451dbbd52f8428b7bb00.pdf 61405_VoR.pdf 2022-10-28T17:03:29.4923621 Output 14278267 application/pdf Version of Record true © The Author(s) 2022. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License true eng https://creativecommons.org/licenses/by-nc/4.0/ |
| title |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
| spellingShingle |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes Steve Luzio Gareth Dunseath Gail Holland Ivy Cheung |
| title_short |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
| title_full |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
| title_fullStr |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
| title_full_unstemmed |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
| title_sort |
Safety of the use of gold nanoparticles conjugated with proinsulin peptide and administered by hollow microneedles as an immunotherapy in type 1 diabetes |
| author_id_str_mv |
01491e1cd582746a654fad9addf0de16 fccbba9edcaee08a839a3c5cff8cbe19 b9f3a8bf7478db012c8856b7bbbc7597 a9142ffd398f89eff40ada503e315639 |
| author_id_fullname_str_mv |
01491e1cd582746a654fad9addf0de16_***_Steve Luzio fccbba9edcaee08a839a3c5cff8cbe19_***_Gareth Dunseath b9f3a8bf7478db012c8856b7bbbc7597_***_Gail Holland a9142ffd398f89eff40ada503e315639_***_Ivy Cheung |
| author |
Steve Luzio Gareth Dunseath Gail Holland Ivy Cheung |
| author2 |
D Tatovic M A McAteer J Barry A Barrientos K Rodríguez Terradillos I Perera E Kochba Y Levin M Dul S A Coulman J C Birchall C von Ruhland A Howell R Stenson M Alhadj Ali Steve Luzio Gareth Dunseath W Y Cheung Gail Holland K May J R Ingram M M U Chowdhury F S Wong R Casas C Dayan J Ludvigsson Ivy Cheung |
| format |
Journal article |
| container_title |
Immunotherapy Advances |
| container_volume |
2 |
| container_issue |
1 |
| publishDate |
2022 |
| institution |
Swansea University |
| issn |
2732-4303 |
| doi_str_mv |
10.1093/immadv/ltac002 |
| publisher |
Oxford University Press (OUP) |
| college_str |
Faculty of Medicine, Health and Life Sciences |
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facultyofmedicinehealthandlifesciences |
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Faculty of Medicine, Health and Life Sciences |
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facultyofmedicinehealthandlifesciences |
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Faculty of Medicine, Health and Life Sciences |
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Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine |
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| description |
Antigen-specific immunotherapy is an immunomodulatory strategy for autoimmune diseases, such as type 1 diabetes, in which patients are treated with autoantigens to promote immune tolerance, stop autoimmune β-cell destruction and prevent permanent dependence on exogenous insulin. In this study, human proinsulin peptide C19-A3 (known for its positive safety profile) was conjugated to ultrasmall gold nanoparticles (GNPs), an attractive drug delivery platform due to the potential anti-inflammatory properties of gold. We hypothesised that microneedle intradermal delivery of C19-A3 GNP may improve peptide pharmacokinetics and induce tolerogenic immunomodulation and proceeded to evaluate its safety and feasibility in a first-in-human trial. Allowing for the limitation of the small number of participants, intradermal administration of C19-A3 GNP appears safe and well tolerated in participants with type 1 diabetes. The associated prolonged skin retention of C19-A3 GNP after intradermal administration offers a number of possibilities to enhance its tolerogenic potential, which should be explored in future studies. |
| published_date |
2022-03-18T04:20:13Z |
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1763754339422175232 |
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11.016235 |