Polymeric drug delivery micelle-like nanocarriers for pulmonary administration of beclomethasone dipropionate

- Beclomethasone dipropionate (BDP)-loaded PHEA-PEG2000-EDA-LA micelles were realised.
- These micelles show proper chemical-physical characteristics for lung administration.
- These micelles were able to permeate through the mucus layer into the lungs.
- In vitro experiments demonstrate that these micelles result highly biocompatible.
- These micelles increase drug uptake on 16-HBE compared to Clenil®.

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 200 nm. Besides, BDP-loaded micelles, obtained with a Drug Loading equal to 5 wt%, 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 44 wt% compared to Clenil® on 16-HBE cells and possess an higher biocompatibility in comparison with the same commercial formulation.

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