Protease-Responsive Hydrogel Microparticles for Intradermal Drug Delivery

Area of Science:

• Biomaterials Science
• Drug Delivery Systems
• Nanotechnology

Background:

• Intradermal drug delivery is crucial for treating skin diseases.
• Developing injectable, sustained-release drug depots is a key challenge.
• Protease-responsive materials offer potential for targeted drug release.

Purpose of the Study:

• To develop protease-responsive microparticles for intradermal drug delivery.
• To evaluate the impact of matrix metalloproteinase 9 (MMP-9) on microparticle properties and drug release.
• To assess the tunability of microparticle characteristics and their safety.

Main Methods:

• Inverse suspension photopolymerization to create multi-arm polyethylene glycol-based microparticles.
• Characterization using scanning electron microscopy and atomic force microscopy.
• In vitro release studies with tofacitinib citrate and cytotoxicity assays with skin fibroblasts.

Main Results:

• Spherical microparticles (∼40 μm) are suitable for intradermal injection (27G needles).
• MMP-9 exposure caused network degradation and reduced elastic moduli.
• Multiple MMP-9 exposures significantly increased tofacitinib citrate release from responsive microparticles.
• Microparticle properties (release profile, elasticity) were tunable by altering polyethylene glycol complexity.
• Cytotoxicity studies showed no adverse effects on skin fibroblasts.

Conclusions:

• Protease-responsive microparticles demonstrate significant potential for controlled intradermal drug delivery.
• The developed microparticles offer tunable drug release profiles and mechanical properties.
• These microparticles are safe for use with skin cells, supporting their therapeutic application.