中文摘要：局部使用抗菌药物治疗中耳炎可以最大限度地提高疗效，并减少副作用。然而，因缺乏给药系统，药物难以通过鼓膜转运。本研究用可变形脂质体包裹MSlys内溶素，用于靶向治疗肺炎链球菌——中耳炎最重要的病原体之一。脂质体组成为：L-α-卵磷脂和胆酸钠（5:1）或L-α-卵磷脂和PEG2000 PE（10:1），MSlys包封率约为35%。PEG脂质体和胆酸钠脂质体的平均流体动力学直径分别为85和115nm，多分散性指数分别为0.32和0.42，在4℃下储存至少一年后均保持稳定。两种脂质体制剂均显示MSlys的缓释超过7天。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MSlys脂质体的生物相容性。此外，微囊化的MSlys对浮游和生物膜肺炎链球菌显示出迅速的抗菌活性，因此对于经鼓室治疗肺炎链球菌中耳炎具有巨大潜力。
外文摘要：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-alphalecithin 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 degrees 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.
外文关键词：endolysin；MSlys；Streptococcus pneumoniae；antibacterial；liposome；drug delivery
作者：Silva, MD；Paris, JL；Gama, FM；Silva, BFB；Sillankorva, S
作者单位：Univ Minho；INL Int Iberian Nanotechnol Lab
期刊名称：ACS INFECTIOUS DISEASES
期刊影响因子：4.614
出版年份：2021
出版刊次：8
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