Introduction: Respiratory infections and diseases are accompanied by or exhibit inflammation. Recent advances in nanoparticle engineering technology, together with the increased knowledge of inflammatory pathophysiology, have ignited interest in the pulmonary delivery of anti-inflammatory agents (AIAs) to achieve local treatment of pulmonary inflammatory disorders. Areas covered: This review summarizes and discusses the investigated formulation approaches for the pulmonary delivery of AIAs, including: inhalation of actives as suspensions or dry powder formulations, with polymeric micro- and nano-delivery carriers, or within liposomes and lipid nanoparticles. Some recent approaches for targeting AIAs to the pulmonary endothelium have also been reviewed. The discussion focuses on finding out whether the investigated approaches were really able to achieve lung targeting and reduce the side effects associated with the systemic administration of AIAs. Expert opinion: The use of the inhalation route for the pulmonary delivery of AIAs is facing several challenges. Some of the investigated formulation approaches appear to be promising in overcoming these challenges. However, in order to create products that reach patients, more therapeutically oriented studies are still needed to ensure formulation stability, in-vivo sustained release behavior, pulmonary retention, and bypassing lung clearance mechanisms.

Formulating nanoparticles for delivery to the deep lung is complex and many techniques fail in terms of nanoparticle stability. Spray freeze drying (SFD) is suggested here for the production of inhalable nanocomposite microcarriers (NCM). Different nanostructures were prepared and characterized including polymeric and lipid nanoparticles. Nanoparticle suspensions were co-sprayed with a suitable cryoprotectant into a cooled, stainless steel spray tower, followed by freeze drying to form a dry powder while equivalent compositions were spray dried (SD) as controls. SFD-NCM possess larger specific surface areas (67–77 m2/g) and lower densities (0.02 g/cm3) than their corresponding SD-NCM. With the exception of NCM of lipid based nanocarriers, SFD produced NCM with a mass median aerodynamic diameter (MMAD) of 3.0 ± 0.5 μm and fine particle fraction (FPF ⩽ 5.2 μm) of 45 ± 1.6% with aerodynamic performances similar to SD-NCM. However, SFD was superior to SD in terms of maintaining the particle size of all the investigated polymeric and lipid nanocarriers following reconstitution (Sf/Si ratio for SFD ≈ 1 versus >1.5 for SD). The SFD into cooled air proved to be an efficient technique to prepare NCM for pulmonary delivery while maintaining the stability of the nanoparticles

Solvent toxicity is one of the major drawbacks in the preparation of polymeric nanoparticles today. Here, polyethylene glycols (PEGs) are proposed as non-toxic solvents for the preparation of polymeric nanoparticles. Based on a preparation process similar to the solvent displacement technique, several process parameters were examined for their effects on the properties of the prepared nanoparticles by this method to achieve the optimum preparation conditions. The investigated parameters included polymer type and concentration, volume and temperature of the dispersing phase, methods of dispersing the solvent phase into the non-solvent phase, duration and speed of stirring and washing by dialysis. Ammonio methacrylate copolymer (Eudragit RL), poly-lactide-co-glycolide (PLGA), and PEG-PLGA were found to be successful polymer candidates for the preparation of nanoparticles by this method. Nanoparticles with diameters ranging from 80 to 400 nm can be obtained. The encapsulation efficiencies of bovine serum albumin, and lysozyme as model proteins were ranging from 7.3 ± 2.2% to 69.3 ± 1.8% depending on the strength of polymer–protein interaction. Biological assays confirmed a full lysozyme activity after the preparation process. PEG proved to be a suitable non-toxic solvent for the preparation of polymeric protein-loaded nanoparticles, maintaining the integrity of protein