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 50 nm) and polymer shell nanocarriers (loading efficiency 25.9 ± 2.3%, size 250 nm). 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 3.2 μg/h to 6.8 μg/h for lipid shell nanocarriers, 2.3 μg/h to 3.4 μg/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 240 nm) 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.