体外评价通过反向全氟碳乳液传递溶血磷脂酸以增强肺泡上皮修复。
In vitro evaluation of lysophosphatidic acid delivery via reverse perfluorocarbon emulsions to enhance alveolar epithelial repair.
机构信息
Department of Biomedical Engineering, Carnegie Mellon University, 5000 Forbes Avenue, Scott Hall 4th Floor, Pittsburgh, PA, 15213, USA.
Department of Medicine, University of Pittsburgh, Division of Pulmonary, Allergy and Critical Care Medicine, East 1200A Biomedical Science Tower, 200 Lothrop Street, Pittsburgh, PA, 15213, USA.
出版信息
Colloids Surf B Biointerfaces. 2018 Sep 1;169:411-417. doi: 10.1016/j.colsurfb.2018.05.037. Epub 2018 May 17.
BACKGROUND
Alveolar drug delivery is needed to enhance alveolar repair during acute respiratory distress syndrome. However, delivery of inhaled drugs is poor in this setting. Drug delivery via liquid perfluorocarbon emulsions could address this problem through better alveolar penetration and improved spatial distribution. Therefore, this study investigated the efficacy of the delivery of lysophosphatidic acid (LPA) growth factor to cultured alveolar epithelial cells via a perfluorocarbon emulsion.
METHODS
Murine alveolar epithelial cells were treated for 2 h with varying concentrations (0-10 μM) of LPA delivered via aqueous solution or PFC emulsion. Cell migration was evaluated 18 h post-treatment using a scratch assay. Barrier function was evaluated 1 h post-treatment using a permeability assay. Proliferation was evaluated 72 h post-treatment using a viability assay.
RESULTS
Partially due to emulsion creaming and stability, the effects of LPA were either diminished or completely hindered when delivered via emulsion versus aqueous. Migration increased significantly following treatment with the 10 μM emulsion (p < 10), but required twice the concentration to achieve an increase similar to aqueous LPA. Both barrier function and proliferation increased following aqueous treatment, but neither were significantly affected by the emulsion.
CONCLUSIONS
The availability and thus the biological effect of LPA is significantly blunted during emulsified delivery in vitro, and this attenuation depends on the specific cellular function examined. Thus, the cellular level effects of drug delivery to the lungs via PFC emulsion are likely to vary based on the drug and the effect it is intended to create.
背景
在急性呼吸窘迫综合征期间，需要肺泡内给药来增强肺泡修复。然而，在这种情况下，吸入药物的传递效果不佳。通过液体全氟碳乳液给药可以通过更好的肺泡穿透和改善空间分布来解决这个问题。因此，本研究通过全氟碳乳液研究了将溶血磷脂酸（LPA）生长因子递送至培养的肺泡上皮细胞的效果。
方法
用不同浓度（0-10 μM）的 LPA 处理 2 h，通过水溶液或 PFC 乳液递送至鼠肺泡上皮细胞。用划痕试验在治疗后 18 h 评估细胞迁移。用通透性试验在治疗后 1 h 评估屏障功能。用活力测定在治疗后 72 h 评估增殖。
结果
部分由于乳液的增稠和稳定性，当通过乳液与水溶液给药时，LPA 的作用要么减弱，要么完全受阻。用 10 μM 乳液处理后迁移显著增加（p<10），但需要两倍的浓度才能达到与水溶液 LPA 相似的增加。水溶液处理后屏障功能和增殖均增加，但乳液均无明显影响。
结论
在体外乳化给药期间，LPA 的可用性和因此其生物学效应显著减弱，这种衰减取决于所检查的特定细胞功能。因此，通过 PFC 乳液向肺部给药的细胞水平效应可能取决于药物及其预期产生的效果。
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