Enhancing immunogenicity of antigens through sustained intradermal delivery using chitosan microneedles with a patch-dissolvable design

Reducing the dosage required for vaccination is highly desirable, particularly in cases of epidemic emergencies. This study evaluated the potential of a chitosan microneedle (MN) system with a patch dissolvable design for low-dose immunization. This system comprises antigen-loaded chitosan MNs and a hydrophilic polyvinyl alcohol/polyvinyl pyrrolidone supporting array patch, which provides extra strength to achieve complete MN insertion and then quickly dissolves in the skin to reduce patch induced skin irritation. After insertion, MNs could be directly implanted in the dermal layer as an intradermal (ID) depot to allow a sustained release of the model antigen ovalbumin (OVA) for up to 28 days. We found that rats immunized with MNs containing low-dose OVA (approximately 200 mu g) had persistently high antibody levels for 18 weeks, which were significantly higher than those observed after an intramuscular injection of full-dose OVA (approximately 500 mu g), demonstrating at least 2.5-fold dose sparing. Moreover, OVA-encapsulated chitosan MNs had superior immunogenicity to OVA plus chitosan solution, indicating that MN-based delivery and prolonged skin exposure can further enhance chitosan's adjuvanticity. Therefore, this patch-dissolvable MN system offers a needle-free, accurate, and reliable ID delivery of antigens and has potential as a sustained ID delivery device to improve vaccine efficacy and facilitate dose sparing with existing vaccines. (c) 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.