Improved Transdermal Delivery of Rabies Vaccine using Iontophoresis Coupled Microneedle Approach

Aim: This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. Methods: Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. Results: Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination (MN_di) compared to MN alone (MN_do). Histological examination of rat skin treated with vaccine laden MN (MN_vo) and MN-iontophoresis combination (MN_vi) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of MN_vo and MN_vi treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after MN_vo and MN_vi treatment, respectively. Conclusion: MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously. Graphical Abstract: [Figure not available: see fulltext.].