Triggered-release nanocapsules for drug delivery to the lungs

• This study demonstrated the feasibility of producing a trigger activated inhaled medicine using solid shelled nanocapsules.
• Pluronic® L62D showed particular specificity for the nanocapsule shell due to suppression of self-aggregation in electrolyte rich fluids.
• Human bronchial epithelial cells tolerated both the trigger system and the nanocapsules which, retained their responsiveness to the trigger when presented to the air–liquid interface generated by the airway cells.

This study demonstrated the feasibility of trigger-responsive inhaled delivery of medicines using soft solid shelled nanocapsules. The delivery system was a 50 nm sized lipid rich capsule carrier that distended rapidly when mixed with an exogenous non-ionic surfactant trigger, Pluronic® L62D. Capsule distension was accompanied by solid shell permeabilisation which resulted in payload release from the carrier; 63.9 ± 16.3% within 1 h. In electrolyte rich aqueous fluids Pluronic® L62D was loosely aggregated, which we suggest to be the cause of its potency in lipid nanocapsule permeabilisation compared to other structurally similar molecules. The specificity of the interaction between L62D and the nanocapsule resulted in carrier payload delivery into human epithelial cells without any adverse effects on metabolic activity or barrier function. This effective, biocompatible, trigger-responsive delivery system provides a versatile platform technology for inhaled medicines.From the Clinical EditorThis study demonstrates the feasibility, efficiency and biocompatibility of trigger-responsive inhaled delivery of 50nm lipid-rich capsule carrier that distends rapidly when mixed with an exogenous non-ionic surfactant trigger, Pluronic L62D.

Solid shell lipid nanocapsules where shown to distend rapidly when incubated with Pluronic® L62. This change, triggered by the surfactant, induced a controllable capsule permeabilisation by inducing shell fluidisation. When the nanocapsules and Pluronic® L62 were applied to the air interface of human bronchial epithelial cells the nanocapsule's chemical payload was delivered effectively into the cells without deleterious effects on the barrier. The triggering mechanism was stable in complex media and the particles have been shown not to induce significant inflammation in vivo in the lungs thus the system was proposed as a viable delivery platform for inhaled medicines.Figure optionsDownload high-quality image (228 K)Download as PowerPoint slide