Spatially Defined Post-manufacturing Loading of Nanoparticles into Hydrogel-Forming Microneedles

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Dermatology

Background:

• Transdermal delivery of genetic material faces challenges due to skin's barrier properties.
• Lipid nanoparticles (LNPs) are effective for mRNA delivery but struggle with skin penetration.
• Hydrogel-forming microneedle (HFMN) patches offer a potential solution, but LNP integration is problematic.

Purpose of the Study:

• To develop and optimize a method for post-manufacturing loading of mRNA-encapsulated LNPs into HFMN patches.
• To evaluate parameters affecting LNP loading efficiency and HFMN integrity.
• To demonstrate successful transdermal delivery of functional LNPs into human skin.

Main Methods:

• Systematic evaluation of HFMN patch height, insertion depth, duration, and repetition using an agarose gel model.
• Loading of MC3-DOPE-DiI-LNPs and MC3-DOPE-eGFP-LNPs into 500 μm HFMN patches.
• Ex vivo experiments with fluorescently labeled LNPs and IVIS imaging for delivery confirmation.

Main Results:

• Optimized loading conditions (500 μm HFMN, 400 μm depth, 15 s hold time, six repetitions) achieved up to 140 μg payload.
• Confirmed nanoparticle release from HFMN patches ex vivo.
• Demonstrated successful cellular uptake of functional LNPs into human skin.

Conclusions:

• The developed method allows robust, spatially controlled, post-manufacturing loading of LNPs into HFMN patches.
• This approach facilitates minimally invasive transdermal delivery of genetic material.
• The findings support the advancement of microneedle-based transdermal gene therapy.