DSPE-PEG polymers for improving pulmonary absorption of poorly absorbed macromolecules in rats and relative mechanism

These findings suggested that these DSPE-PEG polymers are potential for promoting absorptions of poorly absorbable macromolecules with no evidence of damage to the local pulmonary membranes of rats.Novelty statementIn this study, DSPE-PEG-OH and DSPE-PEG-SH polymers, two DSPE-PEG2000 conjugates with different terminal groups demonstrated significant promoting effects on the absorption of poorly absorbed macromolecular drugs after intrapulmonary delivery to rats, and did not induce serious damage to the pulmonary membranes of rats. These DSPE-PEG polymers could statistically downregulate expression levels of tight junction-associated proteins (ZO-1 and occludin), indicating the underlying mechanism by which these polymers exerted their absorption enhancing actions through pulmonary epithelial paracellular pathways. Thus, this study exhibited prospective potential of these DSPE-PEG polymers in developing into dosage forms with the aim to improve the poor bioavailability of some poorly absorbed macromolecular drugs.