Pharmaceutical Nanotechnology
Inhaled nanoparticles—A current review

https://doi.org/10.1016/j.ijpharm.2008.02.011Get rights and content

Abstract

The field of nanotechnology may hold the promise of significant improvements in the health and well being of patients, as well as in manufacturing technologies. The knowledge of this impact of nanomaterials on public health is limited so far. This paper briefly reviews the unique size-controlled properties of nanomaterials, their disposition in the body after inhalation, and the factors influencing the fate of inhaled nanomaterials. The physiology of the lung makes it an ideal target organ for non-invasive local and systemic drug delivery, especially for protein and poorly water-soluble drugs that have low oral bioavailability via oral administration. The potential application of pulmonary drug delivery of nanoparticles to the lungs, specifically in context of published results reported on nanomaterials in environmental epidemiology and toxicology is reviewed in this paper.

Section snippets

Overview of nanomaterials

In the current era of nanoscience, the use of nanotechnologies in commercial applications is increasing in many scientific disciplines, including electronics, sporting goods, tires, stain-resistant clothing, cosmetics, and medicine for diagnosis, imaging and drug delivery.

‘Nanoscience’ and ‘nanotechnologies’ have been defined by the Royal Society and Royal Academy of Engineering (Dowling et al., 2004, Borm et al., 2006b) as follows:

Nanoscience is the study of phenomena and manipulation of

Characteristics of nanomaterials

The main differentiating characteristic of nanomaterials is their size, which falls in the transitional zone between individual atoms or molecules and the corresponding bulk materials (Hoet et al., 2004). Size reduction can modify the physical and chemical properties of nanomaterials distinctively from their bulk and molecular counterparts. It is known that for a group of airborne particles with fixed mass (10 mg/m3) and unit density (1 g/cm3), as the particle size decreases to less than 100 nm,

The lungs as a delivery target for nanomaterials

The lungs, skin and intestinal tract are in direct contact with the environment. These organs are likely to be a first port of entry for nanomaterials into the body. Epidemiological studies showed a positive correlation between increases in atmospheric particulate concentrations and the short-term increases in morbidity and mortality (Borm and Kreyling, 2004, Powell and Kanarek, 2006a). Inhalation is the most significant exposure route for airborne nanoparticles (Hoet et al., 2004, Oberdorster

Deposition of nanomaterials in the respiratory tract

There are three principal mechanisms that lead to pulmonary deposition: inertial impaction, gravitational sedimentation and Brownian diffusion, as summarized in Table 2. The inertial impaction occurs during the passage through the oropharynx and large conducting airways if the particles possess a mass median aerodynamic diameter (MMAD) more than 5 μm. When the MMAD of particles ranges from 1 to 5 μm, they are subject to sedimentation by gravitational force that occurs in smaller airways and

Fate of inhaled nanomaterials in the lung

The fate of inhaled nanomaterials depends on regional distribution in the lung, because disposition within the lung is a complex function of the kinetics of absorption and non-absorptive clearance mechanisms (Sakagami, 2006). Once nanomaterials are deposited onto the lining of the respiratory tract, they first contact the mucous layer within the airways or the surfactant-lining fluid layer within the alveolar region. Airway mucus (about 5 μm in depth) is a complex aqueous secretion of airways,

Systemic translocation of inhaled nanomaterials

Recently, it was reported that inhaled nanomaterials may also influence organs other than the lungs. Inhaled ultrafine technetium (99 mTc) labelled carbon particles, which are very similar to the ultrafine fraction of actual pollutant particles, diffused into the systemic circulation of hamsters within 5 min. Nemmar et al. (2001) concluded that phagocytosis by macrophages and/or endocytosis by epithelial and endothelial cells may be responsible for particle-translocation to the blood, along with

Factors influencing fate of nanomaterials

Clearance of inhaled nanoparticles from the lungs depends mainly on particle size and, by implication, on particle surface characteristics. It was reported following 3 months exposure of rats to ultrafine (∼20 nm) and fine (∼200 nm) titanium dioxide (TiO2) particles by inhalation, the ultrafine particles were cleared significantly more slowly, and showed more translocation to interstitial sites and to regional lymph nodes as compared to the fine TiO2 particles (Oberdorster et al., 1994).

Potential application of nanomaterials in drug delivery

Learning from environmental toxicology studies, nano-sized air pollutants, especially the spherical solid materials, easily enter the lungs and reach the alveoli, and subsequently are cleared from the lungs by different clearance mechanisms. However, due to their small size, nano-sized particles are not likely to be detected around the lung epithelial barriers. They will translocate into systemic circulation and target other organs. Since the definition for the cut-off size of airborne

Delivery devices

Aerosols are an effective method to deliver therapeutic agents to the lungs. Nebulizers, metered dose inhalers (MDIs), or dry powder inhalers (DPIs) are commonly used to generate aerosols (Newman, 1991, Thompson, 1998). Despite the above mentioned advantages of nanoparticles, the use of a drug-bearing nanoparticle itself for delivery to lungs is severely limited because their low inertia causes them to be exhaled after inspiration. Moreover, their small size leads to particle aggregation due to

Pulmonary delivery of therapeutic nanomaterials

Drug-loaded nanoparticles have the potential to be used for pulmonary delivery of therapeutics for treating lung diseases locally and exerting systemic actions. Delivery of therapeutic agents to the site of action for lung diseases may allow for efficient treatment of chronic lung infections, lung cancers, tuberculosis and other respiratory pathologies (Gelperina et al., 2005).

In vivo studies have observed an accumulation of nanoparticles in tumor sites after intravascular administration (

Conclusion

While nanotechnology provides great promises in healthcare, the potential risk imposed by natural and engineered nanomaterials to public health has also been of concern. This is due to their enhanced activity at the nano-scale. The potential of the lung as a natural entry for systemic delivery of aerosols of macromolecules that are otherwise vulnerable to enzyme degradation in the gastro-intestinal tract, and of water-insoluble drugs, has been recognized in the pharmaceutical field. The

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