Environmental Engineering Reference
In-Depth Information
1.4.2.2 Atomic Force Microscopy ........................................................................... 16
1.4.2.3 Electrostatics................................................................................................ 16
1.5 Respiratory Deposition, Retention, and Dosimetry................................................................ 17
1.5.1 Deposition................................................................................................................... 17
1.5.1.1 Gamma Scintigraphy, PET, and SPECT...................................................... 17
1.5.2 Retention ..................................................................................................................... 17
1.5.3 Dosimetry ................................................................................................................... 18
1.5.3.1 Bolus Delivery ............................................................................................. 18
1.5.3.2 Continuous Delivery .................................................................................... 18
1.6 Concluding Remarks .............................................................................................................. 20
References........................................................................................................................................ 21
1.1 
INTRODUCTION
1.1.1  H istorical  P ersPective
The use of aerosol therapy for the treatment of pulmonary disorders can be traced to India over 5000
years ago. 1 These therapies were either palliative, in the form of smokes and mists, or therapeutic,
containing pharmacologically active agents such as stramonium alkaloids. 2 There have been peri-
odic improvements in our understanding of diseases, which give relevance to aerosol approaches.
Modern aerosol therapy with pure drugs was initiated in the 1950s with the development of
the pressurized metered dose inhaler (MDI) for the delivery of β-adrenergic agonists to facilitate
bronchodilatation to relieve the bronchoconstriction occurring in asthmatic patients. 3 In the past 50
years, aerosol therapy has become a central element of asthma management and its potential for the
treatment of other pulmonary and systemic diseases has been explored.
1.1.2  F uture  P rosPects
The future of aerosol therapy seems assured. New developments occur at frequent intervals in the
areas of drug discovery, formulation, and device development. 4,5 The major areas in which new
therapies can be anticipated are treatment of lung diseases such as chronic obstructive pulmonary
disease (COPD), 6 emphysema, 7 lung cancer, 8 and systemic diseases such as diabetes 9 and prostate
cancer. 10
New drugs continue to be developed for the treatment of asthma and COPD such as the anticho-
linergic agent, tiotropium. 11 Undoubtedly, new compounds will be developed as the incidence and
severity of these diseases justiies biomedical research into their underlying causes and mechanisms
of pathogenesis.
Formulation strategies have focused on methods of particle manufacture 12 and desirable physi-
cochemical characteristics. 13,14 These particles can then be placed in one of three general categories
of device: pressurized MDIs, dry powder inhalers (DPIs), or nebulizers. 15 There continue to be new
and exciting developments in each of the categories of device. 5
1.2 
THERAPEUTIC AGENTS
1.2.1  l ocally  a cting  M edical and  P HarMaceutical  a erosols
1.2.1.1  β -Adrenergic Agonists
Figure 1.1a shows the structure of a β-adrenergic agonist. This category of compounds was the
irst to be commercially available for the treatment of the symptom of bronchoconstriction in asth-
matic individuals. The mechanism of action of β 2 -adrenergic agonists is to act on the sympathetic
system to cause muscle relaxation and, therefore, bronchodilation in the lungs. Structurally these
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