IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery

Juha Monkare; M. Reza Nejadnik; Khalil Baccouche; Stefan Romeijn; Wim Jiskoot; Joke A. Bouwstra

doi:10.1016/j.jconrel.2015.10.002

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IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery

Journal article

Open access

Peer reviewed

IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery

Juha Monkare, M. Reza Nejadnik, Khalil Baccouche, Stefan Romeijn, Wim Jiskoot and Joke A. Bouwstra

Journal of controlled release, Vol.218, pp.53-62

11/28/2015

DOI: 10.1016/j.jconrel.2015.10.002

PMID: 26437262

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http://www.sciencedirect.com/science/article/pii/S0168365915301711View

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Abstract

Dissolving microneedles are an attractive approach for non-invasive delivery of drugs via the skin, particularly when the doses are in the microgram or low-milligram range. The aim of the study was to develop hyaluronan-based, monoclonal IgG-loaded microneedles for intradermal delivery enabling efficient penetration and rapid dissolution in the skin while preserving protein stability. Microscopic analysis showed successful preparation of sharp microneedles with the tip length of similar to 280 mu m and with up to 10% (w/w) of IgG content. The water content of the microneedles was similar to 12% and was not affected by the protein content. The protein distribution was uniform within microneedle tips and individual arrays but some array-to-array variation of IgG level within a single preparation batch was detected. After dissolution of microneedle arrays in PBS, >80% of protein was recovered and no conformational changes were detected by fluorescence spectroscopy. At submicron level, only weak and reversible interaction between HA and IgG was found by asymmetric flow field flow fractionation analysis after the dissolution of prepared microneedles. Although, the formation of insoluble micron-size particles was detected by flow imaging microscopy the IgG amount incorporated into these particles was negligible (<5%). Finally, microneedles were able to penetrate into the epidermis of ex vivo human skin followed by the rapid dissolution of the microneedle tips in the skin. After 10 min of application, the majority of the original tip length was dissolved and IgG and hyaluronan were co-deposited until a depth of 150200 mu m in the skin. In conclusion, developed hyaluronan-based dissolving microneedles allow rapid non-invasive intradermal protein delivery. (C) 2015 Elsevier B.V. All rights reserved.

Chemistry

Chemistry, Multidisciplinary

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Physical Sciences

Science & Technology

Details

Title: Subtitle: IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery
Creators: Juha Monkare - Leiden University
M. Reza Nejadnik - Centre for Human Drug Research
Khalil Baccouche - Centre for Human Drug Research
Stefan Romeijn - Leiden University
Wim Jiskoot - Centre for Human Drug Research
Joke A. Bouwstra - Centre for Human Drug Research
Resource Type: Journal article
Publication Details: Journal of controlled release, Vol.218, pp.53-62
DOI: 10.1016/j.jconrel.2015.10.002
PMID: 26437262
NLM abbreviation: J Control Release
ISSN: 0168-3659
eISSN: 1873-4995
Publisher: Elsevier
Number of pages: 10
Grant note: name: Innovative Medicines Initiative Joint Undertaking; name: European Union's Seventh Framework Programme, award: FP7/2007-2013; DOI: 10.13039/100013322, name: EFPIA, award: 115363
Language: English
Date published: 11/28/2015
Academic Unit: Roy J. Carver Department of Biomedical Engineering; Pharmaceutical Sciences and Experimental Therapeutics
Record Identifier: 9984420935202771

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