Abstract
In this paper, the potential of novel polymeric micelles as drug delivery systems for Beclomethasone Dipropionate (BDP) administration into the lung is investigated. These nanostructures are obtained starting from α,β-poly(N-2-hydroxyethyl)-d,l-aspartamide (PHEA), which was subsequently functionalized with O-(2-aminoethyl)-O’-methylpolyethylenglycole (PEG2000), ethylenediamine (EDA) and lipoic acid (LA), obtaining PHEA-PEG2000-EDA-LA graft copolymer. Empty and drug-loaded micelles possess adequate chemical-physical characteristics for pulmonary administration such as spherical shape, slightly positive surface charge and mean size of about 200nm. Besides, BDP-loaded micelles, obtained with a Drug Loading equal to 5wt%, result to be stable in physiological-mimicking media, protecting the drug from hydrolysis and giving a sustained drug release profile. Moreover, the micelle-like structure and surface characteristics seems to improve drug permeation through the mucus layer. Finally, it is also demonstrated that BDP-loaded PHEA-PEG2000-EDA-LA micelles are able to increase cell uptake of BDP of about 44wt% compared to Clenil® on 16-HBE cells and possess an higher biocompatibility in comparison with the same commercial formulation.
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