Department of Biotechnology, Faculty of Applied Sciences, UCSI University, Kuala Lumpur, Malaysia.
Department of Pharmaceutical Sciences, Faculty of Pharmaceutical Sciences, UCSI University, Kuala Lumpur, Malaysia.
PLoS One. 2019 Jul 23;14(7):e0219912. doi: 10.1371/journal.pone.0219912. eCollection 2019.
Vaccine administration via the oral route is preferable to parenteral routes due to ease of administration. To date, most available oral vaccines comprises of live attenuated pathogens as oppose to peptide-based vaccines due to its low bioavailability within the gastrointestinal (GI) tract. Over the years, probiotic-based peptide delivery vehicles comprising of lactic acid bacteria such as Lactococcus lactis has emerged as an interesting alternative due to its generally recognized as safe (GRAS) status, a fully sequenced genome, transient gut colonization time, and is an efficient cellular factory for heterologous protein production. However, its survivability through the GI tract is low, thus better delivery approaches are being explored to improve its bioavailability. In this study, we employ the incorporation of a double coated mucoadhesive film consisting of sodium alginate and Lycoat RS 720 film as the inner coat. The formulated film exhibits good mechanical properties of tensile strength and percent elongation for manipulation and handling with an entrapment yield of 93.14±2.74%. The formulated mucoadhesive film is subsequently loaded into gelatin capsules with an outer enteric Eudragit L100-55 coating capable of a pH-dependent breakdown above pH 5.5 to protect against gastric digestion. The final product and unprotected controls were subjected to in vitro simulated gastrointestinal digestions to assess its survivability. The product demonstrated enhanced protection with an increase of 69.22±0.67% (gastric) and 40.61±8.23% (intestinal) survivability compared to unprotected controls after 6 hours of sequential digestion. This translates to a 3.5 fold increase in overall survivability. Owing to this, the proposed oral delivery system has shown promising potential as a live gastrointestinal vaccine delivery host. Further studies involving in vivo gastrointestinal survivability and mice immunization tests are currently being carried out to assess the efficacy of this novel oral delivery system in comparison to parenteral routes.
口服途径给药优于肠胃外途径给药，因为口服途径给药更容易。迄今为止，大多数可用的口服疫苗由减毒活病原体组成，而不是基于肽的疫苗，因为其在胃肠道 (GI) 中的生物利用度较低。多年来，基于益生菌的肽递送载体，包括乳球菌属乳球菌等乳酸菌，由于其被普遍认为是安全的 (GRAS) 状态、完整的测序基因组、短暂的肠道定植时间以及作为异源蛋白生产的高效细胞工厂，已成为一种有趣的替代方法。然而，其在胃肠道中的存活率较低，因此正在探索更好的递送方法来提高其生物利用度。在这项研究中，我们采用双层包衣粘膜粘附膜，由海藻酸钠和 Lycoat RS 720 膜组成，作为内层。所制备的膜具有良好的机械性能，拉伸强度和伸长率百分比适合操作和处理，包封率为 93.14±2.74%。随后将配制的粘膜粘附膜装入明胶胶囊中，用外层肠溶型 Eudragit L100-55 涂层，在 pH 值高于 5.5 时可发生 pH 依赖性分解，以防止胃消化。将最终产物和未保护的对照物进行体外模拟胃肠道消化，以评估其存活率。与未保护的对照物相比，该产品在经过 6 小时的连续消化后，表现出更好的保护作用，胃存活率增加了 69.22±0.67%（胃）和肠存活率增加了 40.61±8.23%（肠）。这相当于整体存活率提高了 3.5 倍。因此，所提出的口服递送系统作为一种活胃肠疫苗递送宿主具有很大的潜力。目前正在进行涉及体内胃肠存活率和小鼠免疫试验的进一步研究，以评估与肠胃外途径相比，这种新型口服递送系统的功效。
