SOLUTE ABSORPTION FROM THE AIRWAYS OF THE ISOLATED RAT LUNG .4. MECHANISMS OF ABSORPTION OF FLUOROPHORE-LABELED POLY-ALPHA,BETA-[N(2-HYDROXYETHYL)-DL-ASPARTAMIDE]

The pulmonary absorption kinetics of a single molecular weight distrib ution (MWD) of fluorophore-labeled poly-alpha,beta-[N(2-hydroxyethyl)- DL-aspartamide] (FPHEA), a hydrophilic and biocompatible synthetic pol ypeptide, were studied in the isolated, perfused rat lung (iprl) as fu nctions of administered polymer concentration, dose, vehicle, and pres ence and absence of fluorophore. The MWD was characterized before and after absorption by measurement of weight- and number-averaged molecul ar weights (M(w) and M(n), respectively) using high-performance gel-pe rmeation chromatography. Values for M(w) and M(n) were 8.6 and 5.3 kD before, and 6.7 and 4.7 kD after, absorption into the perfusate; there was no significant metabolism and the MWD of the absorbed polymer was independent of both dose and sampling time over a 3-hr period. F-PHEA failed to show any evidence of aggregation in solution or changes in dose distribution within the airways as functions of increasing polyme r concentration and dose. A concentration ranging study indicated the presence of a saturable, carrier-mediated transport process for F-PHEA with a maximum absorption rate, V-max of approximately 180 mu g or 0. 027 mu mol/hr. Coadministration of fluorophore-free PHEA was capable o f depressing the absorption of F-PHEA. The transport process for F-PHE A appeared to have a molecular weight limit of about 7 kD for this hyd rophilic polymer.