Development and characterization of lung surfactant-coated polymer nanoparticles for pulmonary drug delivery

Lung cancer is often diagnosed at an advanced stage where tumors are usually inoperable and first-line therapies are inefficient and have off-targeted adverse effects, resulting in poor patient survival. Here, we report the development of an inhalable poly lactic -co-glycolic acid polymer-based nanoparticle (PLGA-NP) formulation with a biomimetic Infasurf & REG; lung surfactant (LS) coating, for localized and sustained lung cancer drug delivery. The nanoparticles (188 & PLUSMN; 7 nm) were stable in phosphate buffered saline, serum and Gamble's solution (simu-lated lung fluid), and demonstrated cytocompatibility up to 1000 & mu;g/mL concentration and dose-dependent uptake by lung cancer cells. The LS coating significantly decreased nanoparticle (NP) uptake by NR8383 alve-olar macrophages in vitro compared to uncoated NPs. The coating, however, did not impair NP uptake by A549 lung adenocarcinoma cells. The anti-cancer drug gemcitabine hydrochloride encapsulated in the PLGA core was released in a sustained manner while the paclitaxel loaded in the LS shell demonstrated a rapid or burst release profile over 21 days. The drug-loaded NPs significantly decreased cancer cell survival and colony formation in vitro compared to free drugs and single drug-loaded NPs. In vivo studies confirmed greater retention of LS-coated NPs in the lungs of C57BL/6 WT mice compared to uncoated NPs, at 24 h and 72 h following intranasal administration. The overall results confirm that LS coating is a unique strategy for cloaking polymeric NPs to potentially prevent their rapid lung clearance and facilitate prolonged pulmonary drug delivery.