During the last decades the number of therapeutic proteins increased tremendously on the pharmaceutical market. However, due to their often poor stability and limitations of the administration route, the application of therapeutic proteins is a major challenge. The oral mucosa has been suggested as a possible route for protein delivery. In this study, we prepared protein loaded orodispersible films (ODFs), based on blends of trehalose/pullulan by air- and freeze-drying. These two carbohydrates were selected based on the excellent protein stabilizing capacity of trehalose and film-forming ability of pullulan. ODFs were loaded with three model proteins. Ovalbumin was used to study the effect of protein incorporation on the mechanical properties, disintegration time, uniformity of weight and thickness of the ODFs. Lysozyme and β-galactosidase were used to evaluate protein stability. Ovalbumin loading did not significantly influence the mechanical properties of freeze-dried ODFs, while incorporation of ovalbumin in air-dried ODFs led to a substantial reduction in tensile strength. The trehalose/pullulan ratio had no impact on the stability of lysozyme, while the stability of β-galactosidase increased with increasing trehalose/pullulan ratios. Furthermore, freeze-drying appeared to be favorable over air-drying for process stability while the reverse was found for storage stability. In conclusion, trehalose/pullulan-based ODFs are from a technical point promising for possible protein delivery via the oral cavity.

在过去的几十年中，治疗性蛋白质的数量在制药市场上急剧增加。然而，由于它们通常较差的稳定性和给药途径的限制，治疗性蛋白质的应用是主要的挑战。已经提出口腔粘膜是蛋白质递送的可能途径。在这项研究中，我们基于海藻糖/普鲁兰聚糖的混合物，通过风干和冷冻干燥制备了载有蛋白质的口腔分散膜（ODF）。根据海藻糖优异的蛋白质稳定能力和支链淀粉的成膜能力选择这两种碳水化合物。ODF装有三种模型蛋白。卵清蛋白用于研究蛋白质掺入对ODFs的机械性能，崩解时间，重量均匀性和厚度的影响。溶菌酶和β-半乳糖苷酶用于评估蛋白质稳定性。卵清蛋白的负载量不会显着影响冻干ODF的机械性能，而在空气干燥的ODF中掺入卵白蛋白会导致拉伸强度显着降低。海藻糖/普鲁兰比率对溶菌酶的稳定性没有影响，而β-半乳糖苷酶的稳定性随海藻糖/普鲁兰比率的增加而增加。此外，对于过程稳定性而言，冷冻干燥似乎优于空气干燥，而对于储存稳定性则相反。总之，基于海藻糖/普鲁兰聚糖的ODF从技术角度出发有望通过口腔传递蛋白质。而将卵清蛋白掺入风干的ODF中会导致抗张强度大大降低。海藻糖/普鲁兰比率对溶菌酶的稳定性没有影响，而β-半乳糖苷酶的稳定性随海藻糖/普鲁兰比率的增加而增加。此外，对于过程稳定性而言，冷冻干燥似乎优于空气干燥，而对于储存稳定性则相反。总之，基于海藻糖/普鲁兰多糖的ODF从技术角度出发有望通过口腔传递蛋白质。而将卵清蛋白掺入风干的ODF中会导致抗张强度大大降低。海藻糖/普鲁兰比率对溶菌酶的稳定性没有影响，而β-半乳糖苷酶的稳定性随海藻糖/普鲁兰比率的增加而增加。此外，对于过程稳定性而言，冷冻干燥似乎优于空气干燥，而对于储存稳定性则相反。总之，基于海藻糖/普鲁兰多糖的ODF从技术角度出发有望通过口腔传递蛋白质。对于工艺稳定性，冷冻干燥似乎优于风干，而对于储存稳定性则相反。总之，基于海藻糖/普鲁兰多糖的ODF从技术角度出发有望通过口腔传递蛋白质。对于工艺稳定性，冷冻干燥似乎优于风干，而对于储存稳定性则相反。总之，基于海藻糖/普鲁兰多糖的ODF从技术角度出发有望通过口腔传递蛋白质。