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.
Keywords: Cell uptake; Lipoic acid; Mucin permeation; Polyaspartamide; Polymeric micelles; Sustained release.
Copyright © 2016. Published by Elsevier B.V.