Biomedical Engineering Reference
In-Depth Information
Ideal characteristics of nanoformulation
Contain a safe and e cacious drug
Contain minimal quantities of excipients
Small particle size
Monodisperse
High drug loading
Highly reproducible characteristics
Low bioburden
Active
substance
• Particle shape, size
• Molecular weight
• Partition coecient
• Solubility
Improved
pulmonary
response
• Absorption site
• Metabolism, half-life
Clinically
suitable design
of nano-
formulation
Biopharmaceutical
formulation
considerations
Polymers/
amphiphiles
#Particle size
#Zeta potential
#Toxicity
#Cell uptake, efficacy, etc.
FIGURE 11.1
Design of pulmonary drug delivery systems.
both local targeting as well as systemic effect [1,2]. Gene delivery to the lungs is mainly focused on
localized deliveries to the site of action against the genetic disorders affecting the airways such as
antitrypsin deficiency, asthma, and cystic fibrosis, as well as obstructive lung diseases.
11.1.1 p ulMoNary d rug d elIvery : h IstorIcal p rospectIve
The history of engaging the respiratory route for drug delivery dates back to the ancient Egyptian
civilization, when various substances were inhaled either ritually or for healing purposes. Inhalation
therapies engrossed the exploitation of leaves from aromatic plants. With the discovery of liquid
nebulizers around the turn of the twentieth century, this strategy developed into a valid pharma-
ceutical therapy [3,4]. The adrenaline nebulizer solution (1920s), porcine insulin nebulizer (1925s),
pulmonary penicillin (1945s), and steroidal nebulizer (1950s) were among some of the primary
examples in this line. In 1956, the pressurized metered dose inhaler was introduced; along with
advances in molecule design and drug discovery, this route became the mainstay for the treatment
of various disorders [5].
Administration through the pulmonary route has many advantages over other routes for the treat-
ment of particular disease states. Specifically, lung-associated, large protein molecules administered
through an oral route may degrade within the gastrointestinal tract or may be diverted through the
first-pass metabolism into the liver, which can be avoided through the pulmonary route if deposited
in the respiratory passage of the lungs. It must be noted that certain drugs taken by the pulmonary
route are readily absorbed by the alveolar region and then directed into blood circulation. The
pulmonary route has also been investigated as a possible mode of administration for drugs that act
systemically, rather than locally, in the lungs. The driving force behind this was the observation that
peptides and proteins could be absorbed systemically when delivered via the lungs (like morphine,
sildenafil, triptans, etc.) [6-8].
11.1.2 W hy p ulMoNary d rug d elIvery ?
There is an increasing interest in pulmonary drug delivery owing to its high propensity to enhance
the bioavailability of molecules of vivid origins, nature, and molecular weights, in contrast with other
routes of administration (oral, intravenous, buccal, transdermal, rectal, etc.). For the local treatment
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