PLGA-based carriers for pulmonary drug delivery: key concepts Poly(lactic-co-glycolic acid) (PLGA) is not a newcomer in the drug delivery field. Indeed, among the biodegradable polymers currently developed to formulate polymeric drug carriers, PLGA is acknowledged as the most attractive one due to its excellent biocompatibility as well as the possibility to adjust drug delivery features by varying composition, molecular weight and chemical structure. Several PLGA types with very different in vivo lifetimes, ranging from 3 weeks to over a year, are currently approved by US FDA and European Medicine Agency for sustained delivery of drugs via the parenteral route. Nowadays, well-established formulation conditions and methods of production afford the delivery of various types of drugs, in other words, hydrophilic or hydrophobic small molecules as well as macromolecules (peptides, proteins, nucleic acid therapeutics) [1,2]. Lupron Depot, Nutropin Depot, Sandostatin LAR Depot, Somatuline LA, TrelstarTM Depot, Arestin, Risperidal ConstaTM are only some of the PLGA-based products on the market for parenteral administration of drugs. Most of them are intended for sustained release of protein therapeutics (e.g., leuprolide, octreotide, lanreotide, triptorelin), since PLGA-based carriers may effectively protect the macromolecule from in vivo degradation occurring at the administration site [1]. On the other hand, it is now possible to modify the properties of PLGA particles to drive their fate in the biological environment and/or to target the drug to specific organs or cells after administration. PLGA nanocarriers with a size less than 1 μm represent a well-established tool to achieve targeted drug or gene delivery, with special emphasis to cancer treatment [2]. In the attempt to find out novel strategies for the prolonged release of drugs in the lung, PLGA nanoparticles and microparticles are gaining momentum also as carriers for inhalation. A fundamental understanding of the behavior of the particle in biologically relevant conditions as well as an appreciation of in vitro/in vivo effects of the encapsulated drug are essential in the design and development of biodegradable PLGA carriers bearing bioactive agents for therapeutic applications. Indeed, if adequately engineered, PLGA carriers are able to deliver in a sustained manner the intact drug in the airways, to shield its interactions with lung environment and to enhance drug interactions with the cell target [3]. Excellent reviews have recently summarized all the basic requirements of carriers for pulmonary drug delivery [4,5]. The first concern arises from the inhalation device, that is, nebulizer, pressurized metered dose inhaler or dry powder inhaler (DPI). Among them, a great deal of interest was recently aroused in delivering PLGA carriers directly to the lung surfaces via DPIs. This may allow to avoid nebulization resulting in possible instability phenomena (e.g., particle aggrePLGA carriers for inhalation: where do we stand, where are we headed?