Lung-delivered polymer nanoparticles provoked dysfunction of the essential lung surfactant system. A steric shielding of the nanoparticle surface with poloxamers could minimize the unwanted interference of polymer nanoparticles with the biophysical function of lung surfactant. The extent of poly(styrene) and poly(lactide) nanoparticle-induced lung surfactant inhibition could be related to the type and content of the applied poloxamer. Escalations of the adsorbed coating layer thickness (>3 nm) as well as concentration (brush- rather than mushroom-like conformation of poly(ethylene glycol), chain-to-chain distance of <5 nm) on the colloidal surface were capable of circumventing bioadverse effects. Accordingly, specific formulations (i.e., poloxamer 188, 338, and 407) avoided a perturbation of the microstructure and surface activity of Alveofact and a depletion of the content of surfactant-associated proteins. Poloxamer-modified polymer nanoparticles represent a promising nanomedicine platform intended for respiratory delivery revealing negligible effects on the biophysical functionality of the lining layer present in the deep lungs.
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http://dx.doi.org/10.1021/acs.molpharmaceut.7b00477 | DOI Listing |
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