Protein and Peptide Delivery through Respiratory Pathway - Challenges in Delivery of Therapeutic Genomics and Proteomics - page 448

Pulmonary
drug delivery devices

MDI Nebulizer DPI

Standard
inhalers
with
propellants

Spacers and
breath
activated
inhalers

Patient-driven
passive
devices

Battery-driven
active devices

Pneumatic Ultrasonic

Figure 9.3 Pulmonary drug delivery devices (MDI: metered-dose inhaler; DPI: dry powder
inhaler).

are two types of inhalation aerosols, one that allows the deposition of drug
to lungs for systemic effects, and the other whose site of action is primarily localized
in the lung. Therapeutic inhalation aerosols are mainly used in the management of
patients with obstructive lung disease. In the recent past, drug aerosol delivery devices
for inhalable peptides and proteins are garnering increasing interest for the treatment
of systemic and respiratory diseases. These include diabetes and therapies for asthma
and chronic obstructive pulmonary disease (COPD). This advanced technology was
initially applied to the systemic delivery of large molecules, such as insulin, IFN-

There

β , or

α 1 proteinase inhibitor. The first clinical investigation of systemic insulin delivery via

the lung took place in the 1920s, and the interest in this route increased considerably
in recent years with advances in formulation and recombinant technology. The pro-
tein for inhalation currently available on the market is DNase, but a growing number
of proteins and peptides are under various phases of clinical trials. Other proteins and
peptides in Phase III trials include leuprolide and IFN- γ .

9.5.6 Rational Therapy with Inhalation Aerosols
Today 's high potency drugs, proteins, and peptides intended for local and systemic

treatments depend on successful and reliable delivery systems. The rationale for the
development of aerosol drug delivery systems for local and systemic delivery is based
on a multidisciplinary approach to deliver the drug to a specific site and release it,
underpinned by nanoscience and nanotechnology combined with polymer science,
pharmaceutics, bioconjugate chemistry, molecular biology, and other scientific fields.
The

delivery of active pharmaceutical compounds by the oral route remains the most
common method for small molecules but often does not work for macromolecules like
protein and peptides, which are degraded before being absorbed into the bloodstream.
With the exception of DDAVP (9 amino acids) and cyclosporin (11 amino acids), com-
mercially successful oral delivery for peptides and proteins has not been achievable.