title: Controlled drug release from lung-targeted nanocarriers via chemically mediated shell permeabilisation.
abstract: 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.
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors: Hanpeng
authors: H
authors: Chen
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors: Arcadia
authors: A
authors: Woods
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK.
authors: Ben
authors: B
authors: Forbes
authors: Institute of Pharmaceutical Science, Faculty of Life Sciences & Medicine, Franklin-Wilkins Building, King's College London, 150 Stamford Street, London SE1 9NH, UK. Electronic address: stuart.jones@kcl.ac.uk.
authors: Stuart
authors: S
authors: Jones
mesh_terms: D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D016503:Drug Delivery Systems / Q000379:methods*; D065546:Drug Liberation; D008168:Lung / Q000187:drug effects / Q000378:metabolism; D053758:Nanoparticles / Q000008:administration & dosage / Q000737:chemistry* / Q000378:metabolism; D010539:Permeability / Q000187:drug effects; D012293:Rifampin / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism
chemical_list: D003692:Delayed-Action Preparations; D004337:Drug Carriers; D012293:Rifampin
keywords: Controlled drug release; Dissolution; Inhaled drug delivery; Lipid nanoparticles; Poly(vinyl alcohol); Polymer nanoparticles; Rifampicin