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Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives

Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives
Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives

In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device. Light microscopy was used to quality control the printability of the designs, confirming that the actual dimensions are in agreement with the digital design. Non-destructive volume imaging by means of microfocus computed tomography was employed for dimensional and defect characterization of the DLP-printed devices, demonstrating the actual volumes of the reservoirs and the malformations that occurred during printing. The penetration test and finite element analysis showed that the maximum stress experienced by the needles during the insertion process (10 N) was below their ultimate compressive strength (240-310 N). Permeation studies showed the increased permeability of three model drugs when delivered with the MN devices. Size-exclusion chromatography validated the stability of all the actives throughout the permeability tests. The safety of these printed devices for buccal administration was confirmed by histological evaluation and cell viability studies using the TR146 cell line, which indicated no toxic effects.

Administration, Cutaneous, Printing, Three-Dimensional, Skin/metabolism, macromolecules, buccal delivery, microfocus computed tomography, microneedles, hollow, digital light processing, 3D printing
2373-9878
5072-5083
Monou, Paraskevi Kyriaki
5104c7e1-cb4c-4520-8ea4-863a9269c62d
Andriotis, Eleftherios G.
8de232eb-b972-46e0-8dcc-21133536be81
Tsongas, Konstantinos
fecf477a-84e6-454b-8bd3-9d645d60f2c6
Tzimtzimis, Emmanouil K.
3e043894-d2ad-4069-84f6-3f166af70b44
Katsamenis, Orestis L.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Tzetzis, Dimitrios
3b55f4b1-0bcc-4237-b1ba-3108c42fc6c9
Anastasiadou, Pinelopi
8fd22111-8924-4a9b-9848-964ed127884e
Ritzoulis, Christos
9fa4ad95-ee3b-4c42-a0f9-dd72abe34d82
Vizirianakis, Ioannis S.
81fe52f4-d60f-4289-b9e5-332c973df062
Andreadis, Dimitrios
f072f08a-3f54-4fbc-a59e-f7a5f2630d99
Fatouros, Dimitrios G.
4a716c96-a8ba-4fbf-b3db-3b2a3a2794c4
Monou, Paraskevi Kyriaki
5104c7e1-cb4c-4520-8ea4-863a9269c62d
Andriotis, Eleftherios G.
8de232eb-b972-46e0-8dcc-21133536be81
Tsongas, Konstantinos
fecf477a-84e6-454b-8bd3-9d645d60f2c6
Tzimtzimis, Emmanouil K.
3e043894-d2ad-4069-84f6-3f166af70b44
Katsamenis, Orestis L.
8553e7c3-d860-4b7a-a883-abf6c0c4b438
Tzetzis, Dimitrios
3b55f4b1-0bcc-4237-b1ba-3108c42fc6c9
Anastasiadou, Pinelopi
8fd22111-8924-4a9b-9848-964ed127884e
Ritzoulis, Christos
9fa4ad95-ee3b-4c42-a0f9-dd72abe34d82
Vizirianakis, Ioannis S.
81fe52f4-d60f-4289-b9e5-332c973df062
Andreadis, Dimitrios
f072f08a-3f54-4fbc-a59e-f7a5f2630d99
Fatouros, Dimitrios G.
4a716c96-a8ba-4fbf-b3db-3b2a3a2794c4

Monou, Paraskevi Kyriaki, Andriotis, Eleftherios G., Tsongas, Konstantinos, Tzimtzimis, Emmanouil K., Katsamenis, Orestis L., Tzetzis, Dimitrios, Anastasiadou, Pinelopi, Ritzoulis, Christos, Vizirianakis, Ioannis S., Andreadis, Dimitrios and Fatouros, Dimitrios G. (2023) Fabrication of 3D printed hollow microneedles by digital light processing for the buccal delivery of actives. ACS Biomaterials Science & Engineering, 9 (8), 5072-5083. (doi:10.1021/acsbiomaterials.3c00116).

Record type: Article

Abstract

In the present study, two different microneedle devices were produced using digital light processing (DLP). These devices hold promise as drug delivery systems to the buccal tissue as they increase the permeability of actives with molecular weights between 600 and 4000 Da. The attached reservoirs were designed and printed along with the arrays as a whole device. Light microscopy was used to quality control the printability of the designs, confirming that the actual dimensions are in agreement with the digital design. Non-destructive volume imaging by means of microfocus computed tomography was employed for dimensional and defect characterization of the DLP-printed devices, demonstrating the actual volumes of the reservoirs and the malformations that occurred during printing. The penetration test and finite element analysis showed that the maximum stress experienced by the needles during the insertion process (10 N) was below their ultimate compressive strength (240-310 N). Permeation studies showed the increased permeability of three model drugs when delivered with the MN devices. Size-exclusion chromatography validated the stability of all the actives throughout the permeability tests. The safety of these printed devices for buccal administration was confirmed by histological evaluation and cell viability studies using the TR146 cell line, which indicated no toxic effects.

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ab-2023-00116h_Proof_hi - Accepted Manuscript
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Accepted/In Press date: 21 July 2023
e-pub ahead of print date: 1 August 2023
Published date: 1 August 2023
Additional Information: Funding Information: The authors acknowledge the μ-VIS X-ray Imaging Centre at the University of Southampton, founding partner of the UK National Research Facility for lab-based X-ray computed tomography, for the provision of the μCT imaging facilities, data processing, and management infrastructure and expertise. Publisher Copyright: © 2023 American Chemical Society.
Keywords: Administration, Cutaneous, Printing, Three-Dimensional, Skin/metabolism, macromolecules, buccal delivery, microfocus computed tomography, microneedles, hollow, digital light processing, 3D printing

Identifiers

Local EPrints ID: 481405
URI: http://eprints.soton.ac.uk/id/eprint/481405
ISSN: 2373-9878
PURE UUID: a88e690b-f23c-4503-b2c4-457627cb7fae
ORCID for Orestis L. Katsamenis: ORCID iD orcid.org/0000-0003-4367-4147

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Date deposited: 25 Aug 2023 16:45
Last modified: 21 Jul 2024 04:01

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Contributors

Author: Paraskevi Kyriaki Monou
Author: Eleftherios G. Andriotis
Author: Konstantinos Tsongas
Author: Emmanouil K. Tzimtzimis
Author: Dimitrios Tzetzis
Author: Pinelopi Anastasiadou
Author: Christos Ritzoulis
Author: Ioannis S. Vizirianakis
Author: Dimitrios Andreadis
Author: Dimitrios G. Fatouros

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