title: Phospholipid-polyaspartamide micelles for pulmonary delivery of corticosteroids.
abstract: 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 α,β-poly(N-2-hydroxyethyl)-DL-aspartamide (PHEA) with 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethyleneglycol)2000] (DSPE-PEG(2000)-NH(2)). 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 × 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, ζ 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.
authors.affiliation: Lab of Biocompatible Polymers, Dipartimento di Chimica e Tecnologie Farmaceutiche, Università di Palermo, via Archirafi 32, 90123 Palermo, Italy.
authors.forename: Emanuela Fabiola
authors.initials: EF
authors.lastname: Craparo
authors.forename: Girolamo
authors.initials: G
authors.lastname: Teresi
authors.forename: Maria Luisa
authors.initials: ML
authors.lastname: Bondi'
authors.forename: Mariano
authors.initials: M
authors.lastname: Licciardi
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
mesh_terms: D001507:Beclomethasone / Q000008:administration & dosage* / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004337:Drug Carriers / Q000138:chemical synthesis / Q000737:chemistry*; D004339:Drug Compounding; D004355:Drug Stability; D004356:Drug Storage; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008168:Lung / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008823:Micelles; D015394:Molecular Structure; D010316:Particle Size; D010455:Peptides / Q000737:chemistry*; D010714:Phosphatidylethanolamines / Q000138:chemical synthesis / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000138:chemical synthesis / Q000737:chemistry*; D012995:Solubility; D013050:Spectrometry, Fluorescence
chemical_list: C519184:1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-methoxy-poly(ethylene glycol 2000); D004337:Drug Carriers; D008823:Micelles; D010455:Peptides; D010714:Phosphatidylethanolamines; C008965:alpha,beta-poly((2-hydroxyethyl)-aspartamide); D011092:Polyethylene Glycols; D001507:Beclomethasone