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Inhaling medicines: delivering drugs to the body through the lungs

Key Points

  • The use of the lungs for the systemic delivery of medicines is virtually unexploited, and the ancient human practice of inhaling substances for systemic effect (with the exception of anaesthetic gases) has only just begun to be adopted by modern medicine.

  • Inhaled insulin for diabetics was recently approved in the US and Europe and is, so far, the only available inhaled protein-based drug for systemic effect.

  • The high surface area and high permeability of the lungs make them an ideal site for rapid systemic delivery of macromolecules and small-molecule drugs; however, the formulation of the drug is of crucial importance in 'getting the drug to the right place' for optimal absorption.

  • Small molecules are absorbed more rapidly through the lungs than through the gastrointestinal tract, with higher bioavailabilites and reduced first-pass metabolism by enzymes.

  • The lungs are significantly permeable to many peptides and proteins, with the rate of absorption decreasing with increasing molecular mass.

  • Here we review issues in the formulation of drugs that exploit the enormous gas-exchange surface of the lungs as an entry point into the systemic circulation.


Remarkably, with the exception of anaesthetic gases, the ancient human practice of inhaling substances into the lungs for systemic effect has only just begun to be adopted by modern medicine. Treatment of asthma by inhaled drugs began in earnest in the 1950s, and now such 'topical' or targeted treatment with inhaled drugs is considered for treating many other lung diseases. More recently, major advances have led to increasing interest in systemic delivery of drugs by inhalation. Small molecules can be delivered with very rapid action, low metabolism and high bioavailability; and macromolecules can be delivered without injections, as highlighted by the recent approval of the first inhaled insulin product. Here, we review these advances, and discuss aspects of lung physiology and formulation composition that influence the systemic delivery of inhaled therapeutics.

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Figure 1: Comparison of the lung epithelium at different sites within the lungs.
Figure 2: Factors that determine the deposition of inhaled particles.
Figure 3: The alveolocapillary permeability barrier.
Figure 4: The effect of particle size on the deposition of aerosol particles in the human respiratory tract following a slow inhalation and a 5-second breath hold.
Figure 5: Plasma concentration versus time curves following inhalation and injection, illustrating rapid pulmonary absorption.


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Correspondence to John S. Patton.

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Competing interests

J. P. is a co-founder and Chief Scientific Officer of Nektar Therapeutics, a publicly traded company, specializing in pulmonary and PEGylation drug delivery technology.

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Entrez Protein






Type 1 diabetes

Type 2 diabetes





The fraction or percentage of an administered drug or other substance that becomes available to the target tissue or blood after administration. Bioavailability is usually measured against an intravenous dose (absolute bioavailability) but can also be measured against other delivery routes such as subcutaneous injection (relative bioavailability).


A diverse group of tissues that covers or lines nearly all body surfaces, cavities and tubes that function as an interface between different biological compartments. Epithelial layers provide physical protection and containment, and also mediate organ-specific transport properties.

Mucociliary escalator

The self-cleansing system in the airways is composed of a moving epithelial raft of mucus secreted by goblet cells and propelled by ciliated cells. This system serves to move particles that are inhaled and deposited in the lungs up and out into the oesophagus, where material is coughed up and/or swallowed.


Pulmonary macrophages are scavenger cells in the lung derived from monocytes in the circulation. They help keep the lungs clean and although they have the capacity to produce many inflammatory mediators. Macrophages in the airways are relatively non-responsive to foreign materials when compared with other macrophages inside the body.


Proteins embedded in plasma membranes of cells which facilitate the absorption of small or large molecules.

Tight junctions

The complex molecular apparatus that enables cell adhesion in epithelial and endothelial cell sheets. Tight junctions act as a mediator that retards the diffusion of solutes between cells and as a boundary between the apical and basal plasma-membrane domains.


Transport through cell layers by movement directly through the cell cytoplasm (the transcellular pathway), perhaps via membrane vesicles called caveoli, in contrast to transport between cells via the tight junctions (the paracellular pathway).


The plasma membrane vesicles through which transcytosis can occur. These 'little caves' arise by invagination on one side of a cell and carry bound or engulfed material as a membrane vesicle or 'bubble' through the cell's cytoplasm to the other side of the cell. Here, the caveoli can fuse with the plasma membrane and release its cargo to the extracellular space.

Monodisperse particles

Aerosol particles that are all the same size. Most pharmaceutical aerosols are polydisperse. Their particle size is usually expressed as a median diameter surrounded by a spectrum of sizes.

Octanol–water partition coefficients

The equilibrium ratio of concentrations of drug molecules dissolved in an immiscible two-phase solvent system composed of water and octanol (high values reflect lipophilicity).

First-pass metabolism

Usually refers to oral drug administration where metabolism by enzymes in the gastrointestinal wall and liver reduce passage of intact drug into the systemic circulation. Significant amounts of a drug can be lost as it first passes into the body. Pulmonary metabolism of inhaled small-molecule drugs is usually very low compared with oral administration.


A wide range of molecules that are used in pharmaceutical dosage forms to supply one or more of the following functions: add mass and flow properties, improve stability, mask or improve taste, improve injectability, reduce aggregation, improve dispersibility, prolong dissolution and so on.

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Patton, J., Byron, P. Inhaling medicines: delivering drugs to the body through the lungs. Nat Rev Drug Discov 6, 67–74 (2007).

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