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用于口服递送沙门氏菌噬菌体的酸保护聚合物包封制剂的研发。

Development of an Acid-Protective Polymer Encapsulation Formulation for Oral Delivery of Salmonella Phages.

作者信息

Bernela Manju, Virmani Nitin, Bera Bidhan Chand, Vaid Rajesh Kumar, Vashisth Medhavi, Anand Taruna

机构信息

ICAR-National Research Centre on Equines, Hisar 125001, Haryana, India.

National Centre for Veterinary Type Cultures, ICAR-National Research Centre on Equines, Hisar 125001, Haryana, India.

出版信息

Viruses. 2025 Sep 2;17(9):1205. doi: 10.3390/v17091205.

Abstract

Bacteriophage therapy can successfully provide additional treatment to control infection, but low gastric pH limits its oral application. The present study aimed to develop an improved encapsulation formulation with enhanced acid protection for oral delivery of phages using polymers. This was achieved by encapsulating a phage cocktail containing three different bacteriophages against sp. in alginate beads incorporating polyvinyl alcohol (PVA), PVP-K30, and calcium carbonate as viscosity modifiers and acid protection enhancers. Further, the beads were coated with poly-L-lysine to improve the stability and tested for their efficacy for improved phage viability under in vitro acidic conditions for subsequent use in oral delivery. Moist beads were slimy, and semi-dried beads presented a coarse surface as observed using FE-SEM. studies revealed that the free phage cocktail exhibited complete inactivation when exposed to acidic pH 2.5 after 15 min incubation. In contrast, the encapsulated phage cocktail showed a decrease of only 1.66 log units in viability when incubated for 90 min at pH 2.5. Furthermore, oral delivery of the encapsulated phage cocktail in the poultry model significantly reduced bacterial load in infected birds' intestines.

摘要

噬菌体疗法可以成功地提供额外的治疗来控制感染,但胃酸低限制了其口服应用。本研究旨在开发一种改进的包封制剂,使用聚合物增强对口服噬菌体的酸保护。这是通过将含有三种针对特定菌株的不同噬菌体的噬菌体鸡尾酒封装在含有聚乙烯醇(PVA)、PVP-K30和碳酸钙作为粘度调节剂和酸保护增强剂的藻酸盐珠中来实现的。此外,珠子用聚-L-赖氨酸包被以提高稳定性,并测试其在体外酸性条件下提高噬菌体活力的功效,以供后续口服使用。使用场发射扫描电子显微镜观察到,湿珠子是粘滑的,半干珠子表面粗糙。研究表明,游离噬菌体鸡尾酒在pH 2.5的酸性条件下孵育15分钟后完全失活。相比之下,包封的噬菌体鸡尾酒在pH 2.5下孵育90分钟后活力仅下降1.66个对数单位。此外,在家禽模型中口服包封的噬菌体鸡尾酒显著降低了感染鸟类肠道中的细菌载量。

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