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Fabrication of a Master Mold for Microneedles with a Micron-sized Air-vent Hole
Published on: December 5, 2025
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IgG-loaded hyaluronan-based dissolving microneedles for intradermal protein delivery
Juha Mönkäre1, M Reza Nejadnik1, Khalil Baccouche1
1Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research (LACDR), Leiden University, P.O. Box 2300, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Summary
Hyaluronan-based dissolving microneedles successfully deliver monoclonal IgG intradermally. These microneedles efficiently penetrate skin, dissolve rapidly, and preserve protein stability for non-invasive drug delivery.
Area of Science:
- Biomaterials Science
- Drug Delivery Systems
- Nanotechnology
Background:
- Dissolving microneedles offer a promising non-invasive method for transdermal drug delivery, especially for low-dose protein therapeutics.
- Hyaluronan (HA) is a biocompatible polymer suitable for fabricating dissolving microneedles due to its biodegradability and water-retention properties.
Purpose of the Study:
- To develop and characterize hyaluronan-based dissolving microneedles loaded with monoclonal immunoglobulin G (IgG) for efficient intradermal protein delivery.
- To evaluate the microneedles' penetration, dissolution kinetics, protein stability, and deposition profile in ex vivo human skin.
Main Methods:
- Fabrication of hyaluronan microneedles with varying IgG concentrations using micromolding techniques.
- Characterization of microneedle morphology, water content, and IgG distribution using microscopy and spectroscopy.
- Assessment of protein recovery, conformational stability, and interactions post-dissolution using fluorescence spectroscopy and asymmetric flow field flow fractionation.
- Evaluation of skin penetration and dissolution in ex vivo human skin models.
Main Results:
- Sharp, hyaluronan-based microneedles (~280 μm tip length) were successfully fabricated, incorporating up to 10% (w/w) IgG without affecting water content (~12%).
- Uniform IgG distribution was observed within microneedle tips, with minimal protein loss (>80% recovery) and no conformational changes after dissolution.
- Microneedles effectively penetrated ex vivo human epidermis, rapidly dissolving and co-depositing IgG and hyaluronan up to 150-200 μm depth within 10 minutes.
Conclusions:
- Developed hyaluronan-based dissolving microneedles provide a viable platform for rapid, non-invasive intradermal delivery of protein therapeutics like monoclonal IgG.
- The microneedle system preserves protein integrity and demonstrates efficient skin penetration and dissolution, paving the way for advanced biologic delivery.

