Pharmaceutical Technology, Chemical and Biological Engineering, Chalmers University of Technology, SE-41296 Gothenburg, Sweden.
Eur J Pharm Sci. 2012 Nov 20;47(4):695-700. doi: 10.1016/j.ejps.2012.08.014. Epub 2012 Aug 29.
Dry vaccine formulations for sublingual administration would provide great advantages for public health use, especially in developing countries, since they are easy to administer and might also have improved stability properties. This study investigates the influence of protein release rate from mucoadhesive two-layer tablets on the elicited antibody responses after sublingual immunization. Two fast release tablets, one based on a mixture of lactose and microcrystalline cellulose (MCC) and one protein coated ethylcellulose (EC) tablet, and three hydrophilic matrix tablets with extended release (ER) properties based on HPMC 90 SH 100000 or Carbopol® 974-P NF were tested. The in vitro release profiles of the model protein ovalbumin (OVA) from these tablets were characterized and correlated to the in vivo potential of the tablets to induce an immune response after sublingual immunization in BALB/c mice. It could be concluded that a tablet with fast protein release elicits antibody titres not significantly different from titres obtained with OVA in solution, whereas low immune responses were observed with a slow release of OVA from the ER formulations. Thus, an ER tablet seems not favorable for vaccine delivery to the sublingual mucosa. Thus, we can present a fast releasing tablet formulation with attractive features for sublingual immunization, whereas the use of ER formulations for sublingual vaccination has to be investigated more in detail.
经口黏膜给药的干粉疫苗制剂将为公共卫生用途带来巨大优势，尤其是在发展中国家，因为它们易于给药，而且稳定性可能也得到了改善。本研究调查了黏膜黏附双层片剂中蛋白质释放速度对经口黏膜免疫后引发的抗体应答的影响。两种快速释放片剂，一种基于乳糖和微晶纤维素 (MCC) 的混合物，另一种是蛋白质包被的乙基纤维素 (EC) 片剂，以及三种基于 HPMC 90 SH 100000 或 Carbopol® 974-P NF 的具有延长释放 (ER) 性质的亲水性基质片剂进行了测试。对这些片剂中模型蛋白卵清蛋白 (OVA) 的体外释放曲线进行了表征，并将其与片剂经口黏膜免疫后在 BALB/c 小鼠体内引发免疫应答的潜力相关联。可以得出结论，快速释放蛋白质的片剂引发的抗体效价与溶液中 OVA 获得的效价没有显著差异，而 ER 制剂中 OVA 缓慢释放则观察到低免疫应答。因此，对于经口黏膜疫苗输送，ER 片剂似乎并不有利。因此，我们可以提出一种具有经口黏膜免疫吸引力的快速释放片剂制剂，而 ER 制剂用于经口黏膜接种还需要更详细地研究。
