Polyvinyl Alcohol-Coated Polycaprolactone Microneedles as Polymeric Microdevices for Transdermal Antigen Delivery and Immune Activation

Conventional needle-and-syringe vaccination is associated with pain, needle-related anxiety, the need for trained personnel, and logistical challenges related to vaccine distribution and storage. Microneedle (MN) technology has emerged as a minimally invasive strategy for transdermal delivery and as a platform for functional polymeric microdevices. In this study, polycaprolactone (PCL) microneedles coated with hydrophilic polymers were evaluated as a model platform for antigen delivery. Ex vivo assays using porcine ear skin were explored as a preliminary approach to assess antigen transport from polymer-coated PCL microneedles. However, antigen-specific quantification in the receptor compartment was limited by the lack of specificity of absorbance-based measurements in this biological matrix. Scanning electron microscopy (SEM) showed that PVA coating partially altered microneedle tip morphology, whereas optical coherence tomography (OCT) and optical microscopy confirmed that PVA20%-PCL-MNs maintained the ability to insert into porcine skin and generate visible insertion sites. Mechanical compression testing further showed that polymer-coated PCL-MNs maintained resistance to axial deformation under the tested conditions. PVA20%-PCL-MNs were also non-toxic and maintained high HEK293T cell viability after 24 h. Based on their preserved insertion capacity, mechanical robustness, ability to support DNP-KLH permeation, and preliminary cytocompatibility, PVA20%-PCL-MNs were evaluated in BALB/c mice using a two-dose prime-boost regimen. Although intraperitoneal immunization induced higher IgG levels, transdermal immunization with PVA20%-PCL-MNs promoted booster-dependent antigen-specific IgG responses. IgG2a/IgG1 ratio analysis indicated a predominantly IgG1-biased humoral profile, and splenocytes from mice immunized with PVA20%-PCL-MNs produced detectable levels of IFN-γ and IL-10 after in vitro stimulation. Together, these findings support PVA-coated PCL microneedles as a proof-of-concept polymeric microdevice platform for minimally invasive antigen delivery and immunogenicity assessment.