Pulmonary drug administration requires direct delivery of drug formulations into the lower pulmonary tract and alveoli of the lung in the form of inhaled particles or droplets, providing a distinct advantage over other methods for the treatment of respiratory diseases: the drug can be delivered directly to the site of inflammation, thus reducing the need for systemic exposure and the possibility of adverse effects. However, it is difficult to produce droplets of a drug solution within a narrow monodisperse size range (1-10 microm) needed for deposition in the lower pulmonary tract and alveoli. Here, we demonstrate the use of surface acoustic wave microfluidic atomization as an efficient means to generate appropriate aerosols containing a model drug, the short-acting beta2 agonist salbutamol, for the treatment of asthma. The mean aerosol diameter produced, 2.84+/-0.14 microm, lies well within the optimum size range, confirmed by a twin-stage impinger lung model, demonstrating that approximately 70 to 80% of the drug supplied to the atomizer is deposited within the lung. Our preliminary study explores how to control the aerosol diameter and lung delivery efficiency through the surface tension, viscosity, and input power, and also indicates which factors are irrelevant-like the fluid density. Even over a modest power range of 1-1.5 W, SAW atomization provides a viable and efficient generic nebulization platform for the delivery of drugs via the pulmonary route for the treatment of various diseases. The control offered over the aerosol size, low power requirements, high delivery efficiency, and the miniaturization of the system together suggest the proposed platform represents an attractive alternative to current nebulizers compatible with microfluidic technologies.

Extracellular vesicles (EVs)-based therapeutics are based on the premise that EVs shed by stem cells exert similar therapeutic effects and these have been proposed as an alternative to cell therapies. EV-mediated delivery is an effective and efficient system of cell-to-cell communication which can confer therapeutic benefits to their target cells. EVs have been shown to promote tissue repair and regeneration in various animal models such as, wound healing, cardiac ischemia, diabetes, lung fibrosis, kidney injury, and many others. Given the unique attributes of EVs, considerable thought must be given to the preservation, formulation and cold chain strategies in order to effectively translate exciting preclinical observations to clinical and commercial success. This review summarizes current understanding around EV preservation, challenges in maintaining EV quality, and also bioengineering advances aimed at enhancing the long-term stability of EVs.

The novel approach provides a fundamental insight into the cohesive-adhesive balances in dry powder formulations and further understanding of powder behavior.

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This article is based upon the thesis presented to the Faculty of the Graduate School of Cornell University by D. S. Morton in partial fulfilment of the requirements for the degree of Doctor of Philosophy.2 Goldschmidt, Naturwissenschaften, 14, 295 (1926).