LAUSR

Using the pulmonary route for systemic and local drug delivery is an attractive method of drug administration because it has a high alveolar surface area, abundant blood flow, a thin air-blood barrier, and low metabolic activity. In recent years, the evolution of inhalable chitosan nanocomposite microparticles formulations enabled researchers to develop new pulmonary drug delivery platforms that combine the advantages of microparticles and nanoparticles using a biocompatible, biodegradable polymer with polycationic nature and inherent immunogenicity that enhances cell targeting. Therefore, this review aims to offer an overview of the recent advances in inhalable chitosan nanocomposites microparticles formulated in the previous five years in terms of primary nanoparticles manufacturing methods; namely, ionic crosslinking of chitosan using tripolyphosphate, electrospinning/electrospraying, layer-by-layer deposition, and nanospray drying; final microparticles manufacturing techniques using spray drying, nano spray drying, and supercritical assisted spray drying; in addition to the process optimization of the previously mentioned manufacturing methods. Furthermore, this review highlights using chitosan and its derivatives in primary nanoparticles preparation and as a polysaccharide to distribute the prepared nanoparticles in microparticles. Finally, this review discusses the factors affecting yield, encapsulation efficiency, in vitro aerosolization properties, size, morphological characters, in vitro release, and in vivo evaluation of inhalable chitosan nanocomposite microparticles.