Ovalbumin and cholera toxin delivery to buccal mucus for immunization using microneedles and comparison of immunological response to transmucosal delivery.

The oral mucosa is an effective site for vaccination. However, for oral mucosal vaccines, delivery of the right dose of vaccine is not possible due to the water-rich environment. In this study, the buccal mucosa, which is easy to access using a microneedle array in the oral cavity, was selected as the administration site. The immune responses to the use of microneedles to conventional transmucosal delivery were compared. In addition, the adjuvant effect of the addition of cholera toxin (CT) to the drug formulation was observed. Two kinds of patches were prepared: (1) Ovalbumin (OVA) was dip coated only on the tips of microneedles (C-OVA-MN) and (2) OVA was coated on the surface of a flat disk patch substrate without microneedles (C-OVA-D). The drug delivery properties of C-OVA-MN and C-OVA-D were investigated using fluorescent-labeled OVA (OVA/FITC). Each patch was administered to mice twice, 2 weeks apart, and then antibody titers were measured. A microneedle patch can deliver vaccine into the epithelium of the buccal mucosa in a short period of time compared to transmucosal delivery. A microneedle system of C-OVA-MN showed a high serum IgG titer. In addition, CT triggered CD8+ and CD4+ T cell-mediated immune responses. Through this study, we present the possibility of a new method of vaccination to the buccal mucosa using microneedles and CT adjuvant. Illustration of delivery of vaccine to the oral mucosal epithelium using a microneedle patch: Ovalbumin (OVA)-coated microneedle (C-OVA-MN) consists of tip, step, and coating formulation. Microneedle patch coated with OVA formulation is targeting buccal mucosa, which is easy to access in the oral cavity. OVA is delivered to the buccal epithelium precisely using a microneedle patch, and OVA is delivered by transmucosal route using a disk patch.

Microneedle Array Patch (MAP) Consisting of Crosslinked Hyaluronic Acid Nanoparticles for Processability and Sustained Release.

AIMS: Crosslinked hyaluronic acid (X-linked HA) is not suitable for making microneedles because of the low fluidity of X-linked HA hydrogel. Microneedles were fabricated using X-linked HA nanoparticles (X-linked HA-NPs) to utilize the sustained drug delivery capability of X-linked HA-NPs and to obtain the processability advantages of X-linked HA. METHOD: The puncture performance of a microneedle array patch (MAP) made of crosslinked hyaluronic acid nanoparticles (X-linked HA-NP-MAP) was evaluated by insertion in vitro into porcine skin. After a predetermined attachment time, the remaining height of the X-linked HA-NP-MAP was measured to determine the dissolution rate. X-linked HA-NP-MAP and free HA-MAP containing Rhodamine B isothiocyanate-dextran were administered into the back skin of mice, and the relative fluorescent intensity in the back skin was measured over time. RESULTS: The puncture performance of the X-linked HA-NP-MAP was over 90%. The diameter of redispersed X-linked HA-NPs was same as that of the premolded X-linked HA-NPs. The dissolution rate was not different from that of free HA-MAP. In an in vivo experiment, X-linked HA-NP-MAP was administered into the mouse's back skin successfully and the relative fluorescent intensity of X-linked HA-NP-MAP lasted longer than that of HA-MAP. CONCLUSION: X-linked HA-NPs provide the biocompatibility, the processability of micromolding, sustained drug release, successful penetration into the skin, and relatively short insertion time for full disintegration of NPs in the skin. X-linked HA-NP-MAP can be used for various applications that require several days of sustained drug release.