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Sustained Release of a Streptococcus pneumoniae Endolysin from Liposomes for Potential Otitis Media Treatment
ACS Infectious Diseases ( IF 4.0 ) Pub Date : 2021-06-24 , DOI: 10.1021/acsinfecdis.1c00108
Maria Daniela Silva 1, 2 , Juan L Paris 2 , Francisco Miguel Gama 1 , Bruno F B Silva 2 , Sanna Sillankorva 2
Affiliation  

Local delivery of antimicrobials for otitis media treatment would maximize therapeutic efficacy while minimizing side effects. However, drug transport across the tympanic membrane in the absence of a delivery system is challenging. In this study, the MSlys endolysin was encapsulated in deformable liposomes for a targeted treatment of S. pneumoniae, one of the most important causative agents of otitis media. MSlys was successfully encapsulated in liposomes composed of l-alpha-lecithin and sodium cholate (5:1) or l-alpha-lecithin and PEG2000 PE (10:1), with encapsulation efficiencies of about 35%. The PEGylated and sodium cholate liposomes showed, respectively, mean hydrodynamic diameters of 85 and 115 nm and polydispersity indices of 0.32 and 0.42, both being stable after storage at 4 °C for at least one year. Both liposomal formulations showed a sustained release of MSlys over 7 days. Cytotoxicity studies against fibroblast and keratinocyte cell lines revealed the biocompatible nature of both MSlys and MSlys-loaded liposomes. Additionally, the encapsulated MSlys showed prompt antipneumococcal activity against planktonic and biofilm S. pneumoniae, thus holding great potential for transtympanic treatment against S. pneumoniae otitis media.

中文翻译:

从脂质体中持续释放肺炎链球菌内溶素用于潜在的中耳炎治疗

局部递送用于治疗中耳炎的抗微生物剂将最大限度地提高治疗效果,同时最大限度地减少副作用。然而,在没有递送系统的情况下,药物跨鼓膜运输具有挑战性。在这项研究中,MSlys 内溶素被封装在可变形脂质体中,用于靶向治疗肺炎链球菌,这是中耳炎最重要的病原体之一。MSlys 成功封装在由l -α-卵磷脂和胆酸钠 (5:1) 或l组成的脂质体中-α-卵磷脂和 PEG2000 PE (10:1),封装效率约为 35%。聚乙二醇化和胆酸钠脂质体的平均流体动力学直径分别为 85 和 115 nm,多分散指数为 0.32 和 0.42,在 4°C 下储存至少一年后均保持稳定。两种脂质体制剂均显示 MSlys 持续释放超过 7 天。针对成纤维细胞和角质形成细胞系的细胞毒性研究揭示了 MSlys 和装载 MSlys 的脂质体的生物相容性。此外,封装的 MSlys 显示出针对浮游生物和生物膜肺炎链球菌的快速抗肺炎球菌活性,因此具有针对肺炎链球菌中耳炎的跨鼓室治疗的巨大潜力。
更新日期:2021-08-13
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