Faculty of Pharmacy, Bahauddin Zakariya University, Multan, Pakistan.
Leicester School of Pharmacy, De Montfort University, Leicester, UK.
Pharm Res. 2023 Aug;40(8):2039-2049. doi: 10.1007/s11095-023-03521-0. Epub 2023 Apr 25.
This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis.
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.
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) compared to MN alone (MN). Histological examination of rat skin treated with vaccine laden MN (MN) and MN-iontophoresis combination (MN) 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 and MN treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after MN and MN treatment, respectively.
MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously.
本研究旨在开发狂犬病疫苗微针贴片，并评估其与离子电渗法联合应用的免疫原性。
采用真空微压成型技术制备包含聚乙烯吡咯烷酮、透明质酸和聚乙二醇 400 的贴片。通过测定折叠耐力、溶胀率和形态特征对贴片进行物理评估。采用模型药物（亚甲蓝）负载贴片在皮肤模拟琼脂糖凝胶中进行体外释放研究。采用角质层模拟聚偏氟乙烯评估体外插入能力。在大鼠体内进行插入研究。通过测定免疫球蛋白 G（IgG）和狂犬病病毒中和抗体（RVNA）滴度，在犬中评估免疫原性。
贴片显示出具有尖锐尖端和平滑表面的均匀分布微突起，溶胀率约为 70%，可完整折叠约 200 次，并成功穿透聚偏氟乙烯。与单独使用微针（MN）相比，MN-离子电渗联合治疗后（MN）穿过琼脂糖凝胶的模型药物面积几乎增加了一倍。用载有疫苗的 MN（MN）和 MN-离子电渗联合治疗（MN）处理的大鼠皮肤的组织学检查证实，表皮形成了凹槽，而深部血管没有任何损伤。与未处理的对照组相比，MN 和 MN 处理的犬的 IgG 滴度分别增加了约 73%和 206%。MN 和 MN 处理后，RVNA 滴度分别增加了约 1.2 倍和 2.2 倍（与阈值相比）。
MN-离子电渗联合应用提供了比传统肌肉注射更有效的免疫原性反应，因此可用于经皮给药疫苗。
