Sustained antigens delivery using composite microneedles for effective epicutaneous immunotherapy

Area of Science:

• Biomaterials Science
• Immunology
• Nanotechnology

Background:

• Allergen-specific immunotherapy (SIT) is crucial for allergic diseases like food allergy (FA).
• Current SIT methods face challenges with patient compliance due to frequent visits and potential adverse effects.
• Microneedle (MN) technology presents a promising alternative for improved SIT delivery.

Purpose of the Study:

• To develop and evaluate an implantable microneedle (MN) system for allergen-specific immunotherapy (SIT).
• To assess the efficacy and convenience of silk-polyvinyl alcohol (PVA) composite MNs for food allergy (FA) treatment.

Main Methods:

• A two-step casting process was used to create OVA (antigen)-loaded silk microneedles with a dissolvable PVA pedestal.
• The MNs were inserted into the skin, allowing the PVA pedestal to dissolve and implant silk microneedle tips into the dermal layer.
• Immunogenicity and therapeutic effects were evaluated in OVA-sensitized mice, comparing MN immunotherapy to conventional subcutaneous immunotherapy.

Main Results:

• The PVA pedestal dissolved within 5 minutes, implanting silk microneedle tips as a sustained antigen depot.
• MN-based immunotherapy suppressed immune response in OVA-sensitized mice after 3 doses, with no apparent side effects.
• MN immunotherapy was more effective than conventional SIT at a lower antigen dose, demonstrating dose-sparing potential and reduced treatment frequency.

Conclusions:

• The developed implantable silk-PVA composite MNs offer a novel therapeutic strategy for FA treatment.
• This MN system provides prolonged antigen exposure, enhancing efficacy and convenience while reducing treatment frequency.
• The MN-based approach shows significant potential for improving SIT by modulating Th1/Th2 imbalance and ameliorating anaphylaxis.