Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery

Juha Mönkäre; Maria Pontier; Eveline E.M. van Kampen; Guangsheng Du; Mara Leone; Stefan Romeijn; M. Reza Nejadnik; Conor O'Mahony; Bram Slütter; Wim Jiskoot; Joke A. Bouwstra

doi:10.1016/j.ejpb.2018.05.031

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Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery

Journal article

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Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery

Juha Mönkäre, Maria Pontier, Eveline E.M. van Kampen, Guangsheng Du, Mara Leone, Stefan Romeijn, M. Reza Nejadnik, Conor O'Mahony, Bram Slütter, Wim Jiskoot, …

European journal of pharmaceutics and biopharmaceutics, Vol.129, pp.111-121

08/01/2018

DOI: 10.1016/j.ejpb.2018.05.031

PMID: 29803720

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Abstract

[Display omitted] Skin is an attractive but also very challenging immunisation site for particulate subunit vaccines. The aim of this study was to develop hyaluronan (HA)-based dissolving microneedles (MNs) loaded with PLGA nanoparticles (NPs) co-encapsulating ovalbumin (OVA) and poly(I:C) for intradermal immunisation. The NP:HA ratio used for the preparation of dissolving MNs appeared to be critical for the quality of MNs and their dissolution in ex vivo human skin. Asymmetrical flow field-flow fractionation and dynamic light scattering were used to analyse the NPs released from the MNs in vitro. Successful release of the NPs depended on the drying conditions during MN preparation. The delivered antigen dose from dissolving MNs in mice was determined to be 1 µg OVA, in NPs or as free antigen, by using near-infrared fluorescence imaging. Finally, the immunogenicity of the NPs after administration of dissolving MNs (NP:HA weight ratio 1:4) was compared with that of hollow MN-delivered NPs in mice. Immunization with free antigen in dissolving MNs resulted in equally strong immune responses compared to delivery by hollow MNs. However, humoral and cellular immune responses evoked by NP-loaded dissolving MNs were inferior to those elicited by NPs delivered through a hollow MN. In conclusion, we identified several critical formulation parameters for the further development of NP-loaded dissolving MNs.

Dissolving microneedles

Particulate vaccines

PLGA nanoparticles

Skin immunisation

Vaccine delivery

Details

Title: Subtitle: Development of PLGA nanoparticle loaded dissolving microneedles and comparison with hollow microneedles in intradermal vaccine delivery
Creators: Juha Mönkäre - Leiden University
Maria Pontier - Leiden University
Eveline E.M. van Kampen - Leiden University
Guangsheng Du - Leiden University
Mara Leone - Leiden University
Stefan Romeijn - Leiden University
M. Reza Nejadnik - Leiden University
Conor O'Mahony - Leiden University
Bram Slütter - Leiden University
Wim Jiskoot - Leiden University
Joke A. Bouwstra - Leiden University
Resource Type: Journal article
Publication Details: European journal of pharmaceutics and biopharmaceutics, Vol.129, pp.111-121
DOI: 10.1016/j.ejpb.2018.05.031
PMID: 29803720
NLM abbreviation: Eur J Pharm Biopharm
ISSN: 0939-6411
eISSN: 1873-3441
Publisher: Elsevier B.V
Grant note: name: Innovative Medicines Initiative Joint Undertaking, award: 115363; name: European Union's Seventh Framework Programme
Language: English
Date published: 08/01/2018
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984420847202771

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