Drug Targeting Organ-Specific Strategies

lations that not only stabilize the protein, but also deliver it in the adequate physicochemical
state to the absorbing membrane. In addition, it will be necessary to monitor closely the dissolution
rate of drug in order to control the rate of absorption. Only if these requirements are
met, will it be possible for a significant number of potential therapeutic proteins to be administered
by the pulmonary route.
With regard to delivery to the lung, local therapies for asthma or COPD have an established
position. New developments will focus on inhalation devices and formulations that allow
a more reproducible and easy generation of the aerosol cloud and a less critical inhalation
procedure. Generally, improved deposition of the drug in the airways is desirable to improve
dosing accuracy and decrease side-effects. Together with the introduction of new drug
substances technical improvements can still significantly improve the therapy of pulmonary
diseases. For example, a major improvement in the treatment of cystic fibrosis can be
achieved in the coming 5 years due to the development of new inhalation therapies for antibiotic
drugs. Currently, the pulmonary use of about 10 antibiotic drugs has been reported
but only two (tobramycin and colistin) have found a place in regular prophylactic use and
therapy. Moreover, these drugs are still administered by quite inefficient nebulizers that provide
only a deep lung deposition of less than 10% of the administered dose. Both the development
of effective antibiotics against microorganisms such as Pseudomonas aeruginosa and
Burkholderia cepacia as well as the development of innovative formulations and devices to
improve lung deposition can largely optimize antibiotic therapy. Among others, improvements
in this field can lead to better treatment of cystic fibrosis and increase life expectations.
On the longer term, pulmonary administered gene therapy might even further improve cystic
fibrosis therapy.Yet, significant technical hurdles have to be overcome before widespread
use in therapy can be achieved.
In conclusion, it can be stated that the pulmonary administration of drugs is likely to expand
rapidly in the coming years. Yet many questions still exist and extensive basic research
is required before its therapeutic potential can be fully exploited in daily therapeutic practice.
Acknowledgements
Dirk K. F. Meijer is acknowledged for critically reading the manuscript. Bert Stok is thanked
for his help in preparing the reference list.
References
References 83
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