Nanomedicine for Treatment of Acute Lung Injury and Acute Respiratory Distress Syndrome

Sadikot, Ruxana T.; Kolanjiyil, Arun V.; Kleinstreuer, Clement; Rubinstein, Israel

Most of the currently used delivery systems have low predetermined lung-site deposition efficiencies because some drugs are deposited in the device/spacer and much higher amounts in the oral cavity. Hence, direct drug delivery to the required lung sites has become an active research area. With targeted drug delivery, the respiratory drugs can be efficiently administered to the deeper lung regions of interest without any significant loss in the oral/upper airways. Specifically, such targeted delivery of respiratory drugs using modified inhaler devices can be achieved by controlled release of the drug aerosols from the devices. Hence, there is an urgent need to develop aerosol preparations that can be targeted to the lung. So far we have used nanomicellar preparations for the delivery of targeted drugs to the lungs using a systemic approach. Controlled drug delivery systems have also become increasingly attractive options for inhalation therapies [48, 50, 51] . The large surface area of the lungs and the minimal barriers impeding access to the lung periphery make this organ a suitable portal for a variety of therapeutic interventions [14, 52, 53] . The blood barrier between the alveolar space and the pulmonary capillaries is very thin to allow for rapid gas exchange. Alveoli are small and there are approximately 300 million of them in each lung. Although alveoli are tiny structures, they have a very large surface area in total (∼100 m 2 ) for performing efficient gas exchange, making it an attractive organ for direct drug delivery [46, 54] . Among the various drug delivery systems considered for pulmonary application, nanoparticles demonstrate several advantages for the treatment of respiratory diseases, such as prolonged drug release, cell-specific targeted drug delivery, or modified biological distribution of drugs, both at the cellular and organ levels [35, 39, 47, 55] . Nanoparticles composed of biodegradable polymers fulfil many requirements placed on these delivery systems, such as ability to be transferred into an aerosol, stability against forces generated during aerosolization, biocompatibility, targeting of specific sites or cell populations in the lung, release of the drug in a predetermined manner, and degradation within an acceptable period of time [49, 56, 57] .