Phospholipid-polyaspartamide micelles for pulmonary delivery of corticosteroids

A novel drug delivery system for beclomethasone dipropionate (BDP) has been constructed through self-assembly of a pegylated phospholipid-polyaminoacid conjugate. This copolymer was obtained by chemical reaction of alpha,beta-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) with 1,2-distearoyl-snglycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)2000] (DSPE-PEG(2000)-NH2). Benefiting from the amphiphilic structure with the hydrophilic shell based on both PHEA and PEG and many hydrophobic stearoyl tails, PHEA-PEG(2000)-DSPE copolymer was able to self assemble into micelles in aqueous media above a concentration of 1.23 x 10(-7) M, determined by fluorescence studies. During the self-assembling process in aqueous solution, these structures were able to incorporate BDP, with a drug loading (DL) equal to 3.0 wt%. Once the empty and BDP-loaded micelles were prepared, a deep physicochemical characterization was carried out, including the evaluation of mean size, PDI, zeta potential, morphology and storage stability. Moreover, the excellent biocompatibility of both empty and drug-loaded systems was evaluated either on human bronchial epithelium (16HBE) or on red blood cells. The cellular uptake of BDP, free or blended into PHEA-PEG(2000)-DSPE micelles, was also evaluated, evidencing a high drug internalization when entrapped into these nanocarriers and demonstrating their potential for delivering hydrophobic drugs in the treatment of pulmonary diseases. (c) 2010 Elsevier B.V. All rights reserved.