Abstract
The 21st century has seen a paradigm shift to inhaled therapy, for both systemic and local drug delivery, due to the lung's favourable properties of a large surface area and high permeability. Pulmonary drug delivery possesses many advantages, including non-invasive route of administration, low metabolic activity, control environment for systemic absorption and avoids first bypass metabolism. However, because the lung is one of the major ports of entry, it has multiple clearance mechanisms, which prevent foreign particles from entering the body. Although these clearance mechanisms maintain the sterility of the lung, clearance mechanisms can also act as barriers to the therapeutic effectiveness of inhaled drugs. This effectiveness is also influenced by the deposition site and delivered dose. Particulate-based drug delivery systems have emerged as an innovative and promising alternative to conventional inhaled drugs to circumvent pulmonary clearance mechanisms and provide enhanced therapeutic efficiency and controlled drug release. The principle of multiple pulmonary clearance mechanisms is reviewed, including mucociliary, alveolar macrophages, absorptive, and metabolic degradation. This review also discusses the current approaches and formulations developed to achieve optimal pulmonary drug delivery systems.
Highlights
Inhalation therapy has a long and rich history in the treatment of different respiratory diseases using various natural inhalation remedies such as leaves from plants, vapors from aromatic plants, balsams, and myrrh
Results obtained from this study demonstrated that the retention time of cyclosporine A (CsA)-liposomes was 16.9-fold longer than free CsA in normal lung and 7.5-fold longer in inflamed lung[48]
The lung is a very promising target either for local or systemic therapies owing to its large surface area, lower metabolic activity, and the fact that it avoids the first pass metabolism
Summary
Inhalation therapy has a long and rich history in the treatment of different respiratory diseases using various natural inhalation remedies such as leaves from plants, vapors from aromatic plants, balsams, and myrrh. The short halflife and low drug bioavailability of inhaled drugs are due to three main clearance mechanisms (1) pulmonary clearance includes mucociliary clearance and alveolar macrophages, (2) enzymatic degradation, and (3) rapid systemic adsorption[8,10]. This size-discriminating property has been used as a basis for formulating inhalable drugs, which can escape the alveolar macrophages and provide a controlled drug release in the deep lung.
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