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无冷链存储水凝胶可用于婴儿口服阿莫西林治疗肺炎链球菌性肺炎

Cold Chain-Free Storable Hydrogel for Infant-Friendly Oral Delivery of Amoxicillin for the Treatment of Pneumococcal Pneumonia.

机构信息

School of Chemical and Biomedical Engineering, Nanyang Technological University , 70 Nanyang Drive, 637457 Singapore.

School of Biological Sciences, Nanyang Technological University , 60 Nanyang Drive, 637551 Singapore.

出版信息

ACS Appl Mater Interfaces. 2017 Jun 7;9(22):18440-18449. doi: 10.1021/acsami.7b01462. Epub 2017 May 30.

Abstract

Pneumonia is the major cause of death in children under five, particularly in developing countries. Antibiotics such as amoxicillin greatly help in mitigating this problem. However, there is a lack of an infant/toddler-friendly formulation for countries with limited clean water orr electricity. Here, we report the development of a shear-thinning hydrogel system for the oral delivery of amoxicillin to infant/toddler patients, without the need of clean water and refrigeration. The hydrogel formulation consists of metolose (hydroxypropyl methylcellulose) and amoxicillin. It preserves the structural integrity of antibiotics and their antibacterial activity over 12 weeks at room temperature. Pharmacokinetic profiling of mice reveals that the hydrogel formulation increases the bioavailability of drugs by ∼18% compared to that with aqueous amoxicillin formulation. More importantly, oral gavage of this formulation in a mouse model of secondary pneumococcal pneumonia significantly ameliorates inflammatory infiltration and tissue damage in lungs, with a 10-fold reduction in bacterial counts compared to those in untreated ones. Given the remarkable antibacterial efficacy as well as the use of FDA-regulated ingredients (metolose and amoxicillin), the hydrogel formulation holds great promise for rapid clinical translation.

摘要

肺炎是五岁以下儿童死亡的主要原因,特别是在发展中国家。阿莫西林等抗生素在缓解这一问题方面有很大的帮助。然而,对于那些缺乏清洁水或电力的国家来说,儿童友好型的阿莫西林配方制剂却很匮乏。在这里,我们报告了一种剪切变稀水凝胶系统的开发,用于为婴儿/幼儿患者口服输送阿莫西林,无需使用清洁水和冷藏。该水凝胶配方由羟丙甲纤维素(羟丙基甲基纤维素)和阿莫西林组成。它能在室温下保持抗生素的结构完整性及其 12 周的抗菌活性。对小鼠的药代动力学分析显示,与水性阿莫西林制剂相比,水凝胶制剂使药物的生物利用度提高了约 18%。更重要的是,在肺炎链球菌二次肺炎的小鼠模型中,经口服灌胃该制剂可显著减轻肺部炎症浸润和组织损伤,与未治疗的肺部相比,细菌数量减少了 10 倍。鉴于其显著的抗菌效果以及使用 FDA 监管的成分(羟丙甲纤维素和阿莫西林),该水凝胶制剂有望迅速进行临床转化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a114/5465509/9970c619e785/am-2017-01462r_0007.jpg

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