Airway Retention and Pulmonary Absorption of Poly-α,β-[N(2-hydroxyethyl)-D,L-aspartamide]

Abstract

Coarse aqueous sprays of the polymer, poly-α,β-[N(2-hydroxy ethyl)-D,L-aspartamide], (PHEA), containing a covalently bound fluorophore, ethyl carbonyl-6-aminofluorescein, were administered in doses ranging 2.2 through 3.6 mg to the airways of the isolated rat lung (IPRL). The polymer was characterized with number and weight averaged molecular weights of 5300 and 8600 Daltons, respectively. Transfer to the perfusate supplying the pul monary circulation was monitored with time in order to assess the polymer's systemic absorption potential and the transferred molecular weight distribu tions (MWD). The polymer was absorbed at an apparently constant rate during each experiment. The MWD of absorbed material was characterized by gel permeation chromatography and found to be shifted toward lower molecular weights when compared to that of the administered polymer. Two hours after dosing, absorbed material had mean values for weight mean molecular weight, M_w = 6670 ± 526 Daltons and number mean molecular weight, M_n = 4680 ± 640 Daltons where the ranges are standard deviations in 8 IPRL prep arations. PHEA was not metabolized in the 3 h duration of an experiment and there was some tendency for the median molecular weight of the absorbed material to increase with time after administration. Results are discussed in the context of macromolecular delivery to the systemic circulation via the lung.