The purpose of this study was to determine the effect of PEGylation on the interaction of poly(amidoamine) (PAMAM) dendrimer nanocarriers (DNCs) with in vitro and in vivo models of the pulmonary epithelium. Generation-3 PAMAM dendrimers with varying surface densities of PEG 1000 Da were synthesized and characterized. The results revealed that the apical to basolateral transport of DNCs across polarized Calu-3 monolayers increases with an increase in PEG surface density. DNC having the greatest number of PEG groups (n = 25) on their surface traversed at a rate 10-fold greater than its non-PEGylated counterpart, in spite of their larger size. This behavior was attributed to a significant reduction in charge density upon PEGylation. We also observed that PEGylation can be used to modulate cellular internalization. The total uptake of PEG-free DNC into polarized Calu-3 monolayers was 12% (w/w) vs 2% (w/w) for that with 25 PEGs. Polarization is also shown to be of great relevance in studying this in vitro model of the lung epithelium. The rate of absorption of DNCs administered to mice lungs increased dramatically when conjugated with 25 PEG groups, thus supporting the in vitro results. The exposure obtained for the DNC with 25PEG was determined to be very high, with peak plasma concentrations reaching 5 μg·mL^–1 within 3 h. The combined in vitro and in vivo results shown here demonstrate that PEGylation can be potentially used to modulate the internalization and transport of DNCs across the pulmonary epithelium. Modified dendrimers thereby may serve as a valuable platform that can be tailored to target the lung tissue for treating local diseases, or the circulation, using the lung as pathway to the bloodstream, for systemic delivery.

Basidiomycetes (Phylum Basidiomycota) are filamentous fungi characterized by the exogenous formation of spores on a club‐shaped cell called a basidium that are often formed on complex fruiting bodies (mushrooms). Many basidiomycetes serve an important role in recycling lignocellulosic material to higher trophic levels, and some show symbiotic relationships with plants. All known bioluminescent fungi are mushroom‐forming basidiomycetes in the order Agaricales. Hence, the disruption of the basidiomycete community can entirely compromise the carbon cycle in nature from fungi to higher trophic levels. The fungus Gerronema viridilucens was used here to investigate the toxicity of a phenolic compound series based on the inhibition of its bioluminescence. The median effective concentration (EC50) obtained from curves of bioluminescence inhibition versus log[phenolic compound], showed that 2,4,6‐trichlorophenol was the most toxic compound in the series. The logEC50 values of all phenolic compounds were then used for the prediction of their toxicity. The univariate correlation of logEC50 values obtained from six different phenolic compounds was stronger with pK_a than with 1‐octanol‐water partition coefficient (K_ow). Nevertheless, the toxicity can be better predicted by using both parameters, suggesting that the phenol‐driven uncoupling of fungus mitochondrial ATP synthesis is the origin of phenolic compound toxicity to the test fungus.