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A specific and promising approach to limit inflammation and mucin iperproduction in chronic lung diseases relies on specific inhibition of nuclear Factor-κB (NF-κB) by a decoy oligonucleotide (dec-ODN). To fulfill the requirements dictated by translation of dec-ODN therapy in humans, inhalable dry powders were designed on a rational basis to provide drug protection, sustained release and to optimize pharmacological response. To this end, large porous particles (LPP) for dec- ODN delivery made of a sustained release biomaterial (poly(lactic-co-glycolic) acid, PLGA) and an "adjuvant" hydrophilic polymer (polyethylenimine, PEI) were developed and their effects on LPS-stimulated human airway epithelial cells evaluated. The composite PLGA/PEI particles containing dec-ODN (i.e., LPPPEI) were successfully engineered for widespread deposition in the lung and prolonged release of intact dec-ODN in vitro. LPPPEI caused a prolonged inhibition of IL-8 and MUC2 expression in CF human bronchial epithelial cells and human epithelial pulmonary NCI-H292 cells, respectively, as compared to naked dec-ODN. Nonetheless, as compared to previously developed LPP, the presence of PEI was essential to construct a dec-ODN delivery system able to act in mucoepidermoid lung epithelial cells. In perspective, engineering LPP with PEI may become a key factor for tuning carrier properties, controlling lung inflammation and mucin production which, in turn, can foster in vivo translation of dec-ODN therapy. [ABSTRACT FROM AUTHOR]

The development of a novel generation of drug-eluting stent (DES) relies upon the idea to obtain very flexible platforms able to overcome some issues associated to available devices and widen their field of application, especially to the currently emerging biotech therapeutics. Here, we propose a new concept of DES named microsphere-integrated drug-eluting stent (MIDES) composed of drug eluting biodegradable poly( D,L-lactide- co-glycolide) microspheres-encapsulating an hydrophilic model molecule (dextran)-fully integrated in a poly(2-hydroxy-ethyl-methacrylate) coating. By implementing a modified spray-coating technique, we have been able to achieve a thin (10 μm), smooth, and homogeneous hydrogel surface embedding underneath a population of two different microparticles formulations-Dex502H and Dex506. The amount of drug can be tailored, resulting in a dextran loading as high as 1.4 μg/cm, by simply reiteration of coating layer deposition making the MIDES a custom-made device where the release kinetics can be further modified by opportunely choosing microsphere properties. DES use is nowadays restricted to delivery of hydrophobic pharmaceuticals; release of hydrophilic therapeutics from MIDES can, however, be finely controlled by specifically engineering biodegradable microspheres. By varying polymer resomer, we obtained a tunable release rate in the first month of delivery. Depending on the microspheres properties release profile changes drastically moving from a biphasic release, in the case of Dex502H, with a burst of about 20% in the first day to a more sustained release for Dex506 particles. As proof of principle, we also demonstrated that MIDES approach can allows the delivery of two different agents opening up the way to a multitherapy in restenosis treatment. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2011. [ABSTRACT FROM AUTHOR]