Fully embeddable chitosan microneedles as a sustained release depot for intradermal vaccination

Abstract

This study introduces a microneedle transdermal delivery system, composed of embeddable chitosan microneedles and a poly(L-lactide-co-D,L-lactide) (PLA) supporting array, for complete and sustained delivery of encapsulated antigens to the skin. Chitosan microneedles were mounted to the top of a strong PLA supporting array, providing mechanical strength to fully insert the microneedles into the skin. When inserted into rat skin in vivo, chitosan microneedles successfully separated from the supporting array and were left within the skin for sustained drug delivery without requiring a transdermal patch. The microneedle penetration depth was approximately 600 μm (i.e. the total length of the microneedle), which is beneficial for targeted delivery of antigens to antigen-presenting cells in the epidermis and dermis. To evaluate the utility of chitosan microneedles for intradermal vaccination, ovalbumin (OVA; MW = 44.3 kDa) was used as a model antigen. When the OVA-loaded microneedles were embedded in rat skin in vivo, histological examination showed that the microneedles gradually degraded and prolonged OVA exposure at the insertion sites for up to 14 days. Compared to traditional intramuscular immunization, rats immunized by a single microneedle dose of OVA showed a significantly higher OVA-specific antibody response which lasted for at least 6 weeks. These results suggest that embeddable chitosan microneedles are a promising depot for extended delivery of encapsulated antigens to provide sustained immune stimulation and improve immunogenicity.