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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.

DOI:10.3390/v17091205
PMID:41012633
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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本文引用的文献

1
Oral Administration of a Phage Cocktail to Reduce Colonization in Broiler Gastrointestinal Tract-A Pilot Study.口服噬菌体鸡尾酒以减少肉鸡胃肠道中的定植——一项试点研究。
Animals (Basel). 2022 Nov 9;12(22):3087. doi: 10.3390/ani12223087.
2
Use of Phages to Treat Antimicrobial-Resistant Infections in Poultry.噬菌体在治疗家禽抗微生物药物耐药性感染中的应用。
Vet Sci. 2022 Aug 18;9(8):438. doi: 10.3390/vetsci9080438.
3
Antimicrobial Resistance Profiling of Biofilm Forming Non Typhoidal Isolates from Poultry and Its Associated Food Products from Pakistan.
来自巴基斯坦家禽及其相关食品的生物膜形成非伤寒分离株的抗菌药物耐药性分析
Antibiotics (Basel). 2021 Jun 28;10(7):785. doi: 10.3390/antibiotics10070785.
4
Lactobacillus rhamnosus GG defense against Salmonella enterica serovar Typhimurium infection through modulation of M1 macrophage polarization.鼠李糖乳杆菌 GG 通过调节 M1 巨噬细胞极化来防御鼠伤寒沙门氏菌感染。
Microb Pathog. 2021 Jul;156:104939. doi: 10.1016/j.micpath.2021.104939. Epub 2021 May 6.
5
Bacteriophages as Potential Tools for Use in Antimicrobial Therapy and Vaccine Development.噬菌体作为抗菌治疗和疫苗开发的潜在工具
Pharmaceuticals (Basel). 2021 Apr 5;14(4):331. doi: 10.3390/ph14040331.
6
Antimicrobial Resistance and Biofilm Formation Capacity of Serovar Enteritidis Strains Isolated from Poultry and Humans in Poland.从波兰家禽和人类中分离出的肠炎沙门氏菌菌株的抗菌耐药性和生物膜形成能力
Pathogens. 2020 Aug 7;9(8):643. doi: 10.3390/pathogens9080643.
7
The forgotten tale of Brazilian phage therapy.巴西噬菌体疗法被遗忘的故事。
Lancet Infect Dis. 2020 May;20(5):e90-e101. doi: 10.1016/S1473-3099(20)30060-8. Epub 2020 Mar 23.
8
The global burden of non-typhoidal salmonella invasive disease: a systematic analysis for the Global Burden of Disease Study 2017.非伤寒型沙门氏菌侵袭性疾病的全球负担:2017 年全球疾病负担研究的系统分析。
Lancet Infect Dis. 2019 Dec;19(12):1312-1324. doi: 10.1016/S1473-3099(19)30418-9. Epub 2019 Sep 24.
9
The Epidemiology of Monophasic Typhimurium.单相鼠伤寒流行病学。
Foodborne Pathog Dis. 2020 Feb;17(2):87-97. doi: 10.1089/fpd.2019.2676. Epub 2019 Sep 18.
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Encapsulation of E. coli phage ZCEC5 in chitosan-alginate beads as a delivery system in phage therapy.将大肠杆菌噬菌体ZCEC5包裹于壳聚糖-海藻酸盐珠粒中作为噬菌体治疗的递送系统。
AMB Express. 2019 Jun 17;9(1):87. doi: 10.1186/s13568-019-0810-9.