Chen Hanpeng, Woods Arcadia, Forbes Ben, Jones Stuart
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
Int J Pharm. 2016 Sep 25;511(2):1033-41. doi: 10.1016/j.ijpharm.2016.08.012. Epub 2016 Aug 6.
Nanocarriers can aid therapeutic agent administration to the lung, but controlling drug delivery from these systems after deposition in the airways can be problematic. The aim of this study was to evaluate if chemically mediated shell permeabilisation could help manipulate the rate and extent of nanocarrier drug release. Rifampicin was loaded into lipid shell (loading efficiency 41.0±11.4%, size 50nm) and polymer shell nanocarriers (loading efficiency 25.9±2.3%, size 250nm). The drug release at pH 7.4 (lung epithelial pH) and 4.2 (macrophage endosomal pH) with and without the chemical permeabilisers (Pluronic L62D - lipid nanocarriers; H(+)- polymer nanocarriers) was then tested. At pH 7.4 the presence of the permeabilisers increased nanocarrier drug release rate (from 3.2μg/h to 6.8μg/h for lipid shell nanocarriers, 2.3μg/h to 3.4μg/h for polymer shell nanocarriers) and drug release extent (from 50% to 80% for lipid shell nanocarriers, from 45% to 76% for polymer shell nanocarriers). These effects were accompanied by lipid nanocarrier distension (from 50 to 240nm) and polymer shell hydrolysis. At pH 4.2 the polymer nanocarriers did not respond to the permeabiliser, but the lipid nanocarrier maintained a robust drug release enhancement response and hence they demonstrated that the manipulation of controlled drug release from lung-targeted nanocarriers was possible through chemically mediated shell permeabilisation.
纳米载体有助于将治疗剂输送至肺部，但在气道沉积后控制这些系统的药物释放可能存在问题。本研究的目的是评估化学介导的壳层通透性是否有助于控制纳米载体药物释放的速率和程度。将利福平载入脂质壳纳米载体（载药效率41.0±11.4%，粒径50nm）和聚合物壳纳米载体（载药效率25.9±2.3%，粒径250nm）。然后测试在有和没有化学通透剂（泊洛沙姆L62D - 脂质纳米载体；H(+) - 聚合物纳米载体）的情况下，纳米载体在pH 7.4（肺上皮pH值）和4.2（巨噬细胞内体pH值）时的药物释放情况。在pH 7.4时，通透剂的存在提高了纳米载体的药物释放速率（脂质壳纳米载体从3.2μg/h提高到6.8μg/h，聚合物壳纳米载体从2.3μg/h提高到3.4μg/h）以及药物释放程度（脂质壳纳米载体从50%提高到80%，聚合物壳纳米载体从45%提高到76%）。这些效应伴随着脂质纳米载体的膨胀（从50nm到240nm）和聚合物壳的水解。在pH 4.2时，聚合物纳米载体对通透剂无反应，但脂质纳米载体保持了强劲的药物释放增强反应，因此表明通过化学介导的壳层通透性来控制肺靶向纳米载体的药物释放是可行的。
