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Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases

Shunping Han, Rifka N. Utami, Yue Qin, Revadee Liam‐Or, Jemeen Sreedharan, Jeffrey Davies Orcid Logo, Khuloud T. Al‐Jamal Orcid Logo

Small, Volume: 21, Issue: 36, Start page: e04517

Swansea University Author: Jeffrey Davies Orcid Logo

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DOI (Published version): 10.1002/smll.202504517

Abstract

Neurodegenerative diseases remain a major therapeutic challenge in aging populations. Acyl‐ghrelin, a 28‐amino acid gut hormone, demonstrates neuroprotective effects but is limited by instability, rapid clearance, and non‐specific distribution when systemically delivered. Nose‐to‐brain delivery usin...

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ISSN: 1613-6810 1613-6829
Published: Wiley 2025
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URI: https://cronfa.swan.ac.uk/Record/cronfa70073
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Nose&#x2010;to&#x2010;brain delivery using nanotechnology offers a promising alternative. Gold nanorods (AuNRs), with high therapeutics loading capacity, are proposed as carriers for intranasal acyl&#x2010;ghrelin delivery. The previous study demonstrates that intranasal AuNRs effectively reach the brain with minimal systemic exposure. This work investigates the feasibility of using acyl&#x2010;ghrelin gold nanoconjugates to deliver and retain its pharmacological activity through intranasal administration for neurodegenerative diseases. Acyl&#x2010;ghrelin is conjugated via its C&#x2010;terminus to hetero&#x2010;functional polyethylene glycol (PEG) using EDC/sulfo&#x2010;NHS coupling chemistry, then attached to AuNRs through stable Au&#x2500;S bonds. Reaction conditions are optimized to minimize multi&#x2010;PEG substitution, preserving acyl&#x2010;ghrelin bioactivity and preventing AuNR cross&#x2010;linking. 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spelling 2026-01-23T11:31:52.8982821 v2 70073 2025-07-31 Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases 2cb3d1d96a7870a84d2f758e865172e6 0000-0002-4234-0033 Jeffrey Davies Jeffrey Davies true false 2025-07-31 MEDS Neurodegenerative diseases remain a major therapeutic challenge in aging populations. Acyl‐ghrelin, a 28‐amino acid gut hormone, demonstrates neuroprotective effects but is limited by instability, rapid clearance, and non‐specific distribution when systemically delivered. Nose‐to‐brain delivery using nanotechnology offers a promising alternative. Gold nanorods (AuNRs), with high therapeutics loading capacity, are proposed as carriers for intranasal acyl‐ghrelin delivery. The previous study demonstrates that intranasal AuNRs effectively reach the brain with minimal systemic exposure. This work investigates the feasibility of using acyl‐ghrelin gold nanoconjugates to deliver and retain its pharmacological activity through intranasal administration for neurodegenerative diseases. Acyl‐ghrelin is conjugated via its C‐terminus to hetero‐functional polyethylene glycol (PEG) using EDC/sulfo‐NHS coupling chemistry, then attached to AuNRs through stable Au─S bonds. Reaction conditions are optimized to minimize multi‐PEG substitution, preserving acyl‐ghrelin bioactivity and preventing AuNR cross‐linking. The resulting nanoconjugates successfully deliver ghrelin to the brain, reaching peak levels at 10 min post‐administration with ≈2067.6 ± 760.6 pg g−1 of brain, a fourfold increase over native expression. Importantly, the peptide retains biological function, as evidenced by AMPK phosphorylation at 30–60 min, a key marker of ghrelin‐induced neuroprotection. These findings support intranasal AuNR‐mediated delivery of acyl‐ghrelin as a promising strategy for treating neurodegenerative diseases. Journal Article Small 21 36 e04517 Wiley 1613-6810 1613-6829 acyl-ghrelin peptide, brain uptake, gold nanorods, intranasal administration, neurodegenerative diseases 1 9 2025 2025-09-01 10.1002/smll.202504517 COLLEGE NANME Medical School COLLEGE CODE MEDS Swansea University Another institution paid the OA fee Biotechnology and Biological Sciences Research Council. Grant Number: BB/J008656/1; Brain Tumour Charity. Grant Number: GN-000398; Indonesian Endowment Fund for Education; Wellcome Trust. Grant Numbers: WT103913, 221824/Z/20/Z; King's College London; China Scholarship Council 2026-01-23T11:31:52.8982821 2025-07-31T11:57:58.5668739 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Biomedical Science Shunping Han 1 Rifka N. Utami 2 Yue Qin 3 Revadee Liam‐Or 4 Jemeen Sreedharan 5 Jeffrey Davies 0000-0002-4234-0033 6 Khuloud T. Al‐Jamal 0000-0001-5165-2699 7 70073__34884__7d60ed3d353b4459ae0d0b5f4c3e9606.pdf 70073.VOR.pdf 2025-07-31T12:05:32.1819041 Output 1253207 application/pdf Version of Record true © 2025 The Author(s). This is an open access article under the terms of the Creative Commons Attribution License (CC BY). true eng http://creativecommons.org/licenses/by/4.0/
title Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases
spellingShingle Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases
Jeffrey Davies
title_short Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases
title_full Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases
title_fullStr Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases
title_full_unstemmed Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases
title_sort Nose‐to‐Brain Delivery of Acyl‐Ghrelin Peptide Gold Nanoconjugates for Treatment of Neurodegenerative Diseases
author_id_str_mv 2cb3d1d96a7870a84d2f758e865172e6
author_id_fullname_str_mv 2cb3d1d96a7870a84d2f758e865172e6_***_Jeffrey Davies
author Jeffrey Davies
author2 Shunping Han
Rifka N. Utami
Yue Qin
Revadee Liam‐Or
Jemeen Sreedharan
Jeffrey Davies
Khuloud T. Al‐Jamal
format Journal article
container_title Small
container_volume 21
container_issue 36
container_start_page e04517
publishDate 2025
institution Swansea University
issn 1613-6810
1613-6829
doi_str_mv 10.1002/smll.202504517
publisher Wiley
college_str Faculty of Medicine, Health and Life Sciences
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hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Biomedical Science{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Biomedical Science
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description Neurodegenerative diseases remain a major therapeutic challenge in aging populations. Acyl‐ghrelin, a 28‐amino acid gut hormone, demonstrates neuroprotective effects but is limited by instability, rapid clearance, and non‐specific distribution when systemically delivered. Nose‐to‐brain delivery using nanotechnology offers a promising alternative. Gold nanorods (AuNRs), with high therapeutics loading capacity, are proposed as carriers for intranasal acyl‐ghrelin delivery. The previous study demonstrates that intranasal AuNRs effectively reach the brain with minimal systemic exposure. This work investigates the feasibility of using acyl‐ghrelin gold nanoconjugates to deliver and retain its pharmacological activity through intranasal administration for neurodegenerative diseases. Acyl‐ghrelin is conjugated via its C‐terminus to hetero‐functional polyethylene glycol (PEG) using EDC/sulfo‐NHS coupling chemistry, then attached to AuNRs through stable Au─S bonds. Reaction conditions are optimized to minimize multi‐PEG substitution, preserving acyl‐ghrelin bioactivity and preventing AuNR cross‐linking. The resulting nanoconjugates successfully deliver ghrelin to the brain, reaching peak levels at 10 min post‐administration with ≈2067.6 ± 760.6 pg g−1 of brain, a fourfold increase over native expression. Importantly, the peptide retains biological function, as evidenced by AMPK phosphorylation at 30–60 min, a key marker of ghrelin‐induced neuroprotection. These findings support intranasal AuNR‐mediated delivery of acyl‐ghrelin as a promising strategy for treating neurodegenerative diseases.
published_date 2025-09-01T06:55:43Z
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