Innovative transdermal delivery of insulin using gelatin methacrylate-based microneedle patches in mice and mini-pigs
Bilal Demir
(1, 2, 3)
,
Lea Rosselle
(2)
,
Anna Voronova
(2)
,
Quentin Pagneux
,
Audrey Quenon
(4)
,
Valery Gmyr
(4)
,
Dorothee Jary
,
Nathalie Hennuyer
,
Bart Staels
,
Thomas Hubert
(4)
,
Amar Abderrahmani
(2, 5)
,
Valérie Plaisance
(2, 5)
,
Valérie Pawlowski
(2, 5)
,
Rabah Boukherroub
(2, 5)
,
Severine Vignoud
(3)
,
Sabine Szunerits
(2, 5)
1
CEA-TECH-Reg -
CEA Tech en régions
2 IEMN - Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520
3 DTBS - Département Microtechnologies pour la Biologie et la Santé
4 EGID - Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
5 NBI - IEMN - NanoBioInterfaces - IEMN
2 IEMN - Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520
3 DTBS - Département Microtechnologies pour la Biologie et la Santé
4 EGID - Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
5 NBI - IEMN - NanoBioInterfaces - IEMN
Quentin Pagneux
- Fonction : Auteur
Valery Gmyr
- Fonction : Auteur
- PersonId : 800270
- ORCID : 0000-0003-1236-359X
- IdRef : 122344030
Dorothee Jary
- Fonction : Auteur
Nathalie Hennuyer
- Fonction : Auteur
- PersonId : 760862
- ORCID : 0000-0003-0303-7258
Bart Staels
- Fonction : Auteur
- PersonId : 735802
- IdHAL : bart-staels
- ORCID : 0000-0002-3784-1503
- IdRef : 075009838
Amar Abderrahmani
- Fonction : Auteur
- PersonId : 747981
- IdHAL : amar-abderrahmani
Valérie Plaisance
- Fonction : Auteur
- PersonId : 748004
- IdHAL : valerie-plaisance
Valérie Pawlowski
- Fonction : Auteur
- PersonId : 1298310
- IdHAL : valeriepawlowski
- ORCID : 0000-0002-7708-7517
Rabah Boukherroub
- Fonction : Auteur
- PersonId : 177969
- IdHAL : rabah-boukherroub
- ORCID : 0000-0002-9795-9888
- IdRef : 139279474
Severine Vignoud
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 1125557
Connectez-vous pour contacter l'auteur
Sabine Szunerits
Connectez-vous pour contacter l'auteur
- Fonction : Auteur correspondant
- PersonId : 21321
- IdHAL : sabine-szunerits
- ORCID : 0000-0002-1567-4943
- IdRef : 097506362
Connectez-vous pour contacter l'auteur
Résumé
Painless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. , Painless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. To achieve this purpose, microneedle patches are gaining increased attention. While degradable microneedle (MN) arrays are widely employed, the use of non-dissolving MN patches remains a challenge to overcome. In this study, we demonstrate that crosslinking gelatin methacrylate with polyethylene glycol diacrylate (PEGDA) is potent for engineering non-dissolving MN arrays. Incorporation of MoS 2 nanosheets as a photothermal component into MN hydrogels results in MNs featuring on-demand release properties. An optimized MoS 2 -MN array patch formed using a hydrogel solution containing 500 μg mL −1 of MoS 2 and photochemically crosslinked for 5 min shows required mechanical behavior under a normal compressive load to penetrate the stratum corneum of mice or pig skin and allows the delivery of macromolecular therapeutics such as insulin upon swelling. Using ex vivo and in vivo models, we show that the MoS 2 -MN patches can be used for loading and releasing insulin for therapeutic purposes. Indeed, transdermal administration of insulin loaded into MoS 2 -MN patches reduces blood glucose levels in C57BL/6 mice and mini-pigs comparably to subcutaneously injected insulin. We believe that this on-demand delivery system might alter the current insulin therapies and might be a potential approach for delivery of other proteins.
Format du dépôt | Notice |
---|---|
Type de dépôt | Article dans une revue |
Titre |
en
Innovative transdermal delivery of insulin using gelatin methacrylate-based microneedle patches in mice and mini-pigs
|
Résumé |
en
Painless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. , Painless and controlled on-demand drug delivery is the ultimate goal for the management of various chronic diseases, including diabetes. To achieve this purpose, microneedle patches are gaining increased attention. While degradable microneedle (MN) arrays are widely employed, the use of non-dissolving MN patches remains a challenge to overcome. In this study, we demonstrate that crosslinking gelatin methacrylate with polyethylene glycol diacrylate (PEGDA) is potent for engineering non-dissolving MN arrays. Incorporation of MoS 2 nanosheets as a photothermal component into MN hydrogels results in MNs featuring on-demand release properties. An optimized MoS 2 -MN array patch formed using a hydrogel solution containing 500 μg mL −1 of MoS 2 and photochemically crosslinked for 5 min shows required mechanical behavior under a normal compressive load to penetrate the stratum corneum of mice or pig skin and allows the delivery of macromolecular therapeutics such as insulin upon swelling. Using ex vivo and in vivo models, we show that the MoS 2 -MN patches can be used for loading and releasing insulin for therapeutic purposes. Indeed, transdermal administration of insulin loaded into MoS 2 -MN patches reduces blood glucose levels in C57BL/6 mice and mini-pigs comparably to subcutaneously injected insulin. We believe that this on-demand delivery system might alter the current insulin therapies and might be a potential approach for delivery of other proteins.
|
Auteur(s) |
Bilal Demir
1, 2, 3
, Lea Rosselle
2
, Anna Voronova
2
, Quentin Pagneux
, Audrey Quenon
4
, Valery Gmyr
4
, Dorothee Jary
, Nathalie Hennuyer
, Bart Staels
, Thomas Hubert
4
, Amar Abderrahmani
2, 5
, Valérie Plaisance
2, 5
, Valérie Pawlowski
2, 5
, Rabah Boukherroub
2, 5
, Severine Vignoud
3
, Sabine Szunerits
2, 5
1
CEA-TECH-Reg -
CEA Tech en régions
( 255534 )
- CEA Grenoble
17 rue des Martyrs
38054 Grenoble Cedex 9
- France
2
IEMN -
Institut d’Électronique, de Microélectronique et de Nanotechnologie - UMR 8520
( 1066983 )
- [Univ. Lille, CNRS, Centrale Lille Institut, Junia, Univ. Polytechnique Hauts-de-France] ––
Laboratoire Central – Cité Scientifique – Avenue Poincaré – CS 60069 – 59652 VILLENEUVE D’ASCQ CEDEX
- France
3
DTBS -
Département Microtechnologies pour la Biologie et la Santé
( 40213 )
- France
4
EGID -
Institut Européen de Génomique du Diabète - European Genomic Institute for Diabetes - FR 3508
( 508049 )
- Pôle Recherche
1er étage Aile Ouest
1 place de Verdun
59045 Lille Cedex
- France
5
NBI - IEMN -
NanoBioInterfaces - IEMN
( 1067477 )
- Groupe NBI - CCHB IRCICA - 50 Avenue Halley - 59650 Villeneuve d'Ascq
- France
|
Langue du document |
Anglais
|
Audience |
Internationale
|
Volume |
7
|
Page/Identifiant |
174-184
|
URL éditeur |
http://xlink.rsc.org/?DOI=D1NH00596K
|
Nom de la revue |
|
Vulgarisation |
Non
|
Comité de lecture |
Oui
|
Date de publication |
2022-02-01
|
Date de publication électronique |
2021-12-22
|
Numéro |
2
|
Domaine(s) |
|
Référence interne |
|
Financement |
|
DOI | 10.1039/D1NH00596K |
UT key WOS | 000743590200001 |
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