Journal
MOLECULAR PHARMACEUTICS
Volume 14, Issue 10, Pages 3464-3472Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.molpharmaceut.7b00477
Keywords
biophysical inhibition; lung surfactant; PEGylation; poloxamer; polymer nanoparticles
Funding
- Deutsche Forschungsgemeinschaft [BE 5308/1-1, RU 1866/1-2]
- Wirtschafts- und Infrastrukturbank Hessen (Nanosurfact)
- Danish Council for Independent Research [DFF-12-131927]
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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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