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Figure 1. Hypothetical outcomes of altering the physicochemical properties of carbon nanotubes for drug delivery. Inhaled pristine CNTs aggregate and are taken up by macrophages, where they stimulate ROS generation and activation of the inflammasome to produce IL-1β, a proximal mediator of pulmonary fibrosis. Purifying CNTs to remove residual metal catalysts reduces ROS, macrophage activation and fibrosis. Functionalization of CNTs to increase dispersability and modify biodegradation would be needed for drug delivery and could result in evasion of macrophage uptake and increased bioavailability. Further functionalization could involve attachment of therapeutic agents and allowing for cell-specific targeting. The ultimate success of using CNTs as a drug-delivery platform would depend on the risk of side effects (fibrosis or cancer) in relation to effective therapy of a particular disease. CNT: Carbon nanotube; ROS: Reactive oxygen species.
(Figure omitted. See article PDF.)
Figure 2. Postulated susceptibility factors to carbon nanotube exposure and associated pathologic or physiologic consequences. Mouse models of susceptibility have been used to demonstrate that pre-existing inflammation induced by allergens to induce experimental asthma, bacterial wall products or bacterial infection increase lung fibrogenic reactions to CNTs. Factors that influence CNT-induced exacerbation of pre-existing disease include reduced mucociliary clearance of CNTs in asthma or COPD, and enhanced inflammation by CNTs when combined with microbial infection. Susceptibility genes also probably play an important role in determining severity of disease outcome in response to CNTs. CNT: Carbon nanotube; COPD: Chronic obstructive pulmonary disease.
(Figure omitted. See article PDF.)
Nanotechnology offers significant benefits for improving drug delivery and therapy of respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis. Nanoparticles (NPs) have been of great interest for some time as they can be designed to simultaneously carry a drug payload, specifically target features of diseased tissues and carry an imaging molecule to track drug accumulation and clearance in tissues. Moreover, they can be engineered for more sustained drug delivery to improve pharmacokinetics and reduce the overall amount of drug administered during treatment of disease. A variety of NPs have been investigated in experimental animal models as tools to improve the therapeutic efficacy of drugs or genes delivered to the lung or other organ systems [1]. The nanotechnology platform for drug delivery contains a number of very different...