Sustainable strategies for nano-in-micro particle engineering for pulmonary delivery

With the increasing popularity and refinement of inhalation therapy, there has been a huge demand for the design and development of fine-tuned inhalable drug particles capable of assuring an efficient delivery to the lungs with optimal therapeutic outcomes. To cope with this demand, novel particle technologies have arisen over the last decade agreeing with the progress of pulmonary therapeutics that were commonly given by injection. Nanotechnology holds a considerable potential in the development of new release mechanisms of active ingredients to the deep lungs. For an accurate deep lung deposition and effective delivery of nanoparticles, respirable nano-in-micro formulations have been extensively investigated. Microparticles with nanoscale features can now be developed, and their functionalities have contributed to stabilize and improve the efficacy of the particulated dosage form. This paper reviews the different types of the aerosolizable nano-in-micro particles, as well as their sustainable production and characterization processes as dry powders. This review also intends to provide a critical insight of the current goals and technologies of particle engineering for the development of pulmonary drug delivery systems with a special emphasis on nano-micro dry powder formulations prepared by spray-drying and supercritical fluid-assisted techniques. The merits and limitations of these technologies are debated with reference to their appliance to specific drug and/or excipient materials. Finally, a list of most recent/ongoing clinical trials regarding pulmonary delivery of this type of formulation is described.