1. Introduction

In recent decades, with the continuous development of medical technology, people have achieved an in-depth understanding of lung functions and characteristics. Pulmonary administration has been recognized as a simple and effective method for treating lung and other diseases [1–3]. The drug delivery system (DDS), which transports drugs directly to the lung to produce local or systemic therapeutic effects, is known as the pulmonary drug delivery system (PDDS). Oral drugs need to be absorbed by the gastrointestinal tract and further transported through the blood circulation to reach the lesion site. In this series of complex processes, serious drug loss happens after confronting acid, alkali, enzyme degradation, and liver elimination. Ultimately, only a small amount of drugs can reach the lesion site, which seriously reduces the drug bioavailability and impairs the therapeutic outcomes [4]. Parenteral administration can cause damage to the tissue and reduce patient compliance. By contrast, PDDS can deliver the drugs directly to the lung

through the trachea for the local treatment of lung diseases. Compared with systemic administration, pulmonary administration is an ideal way for treating lung disease. It can significantly reduce the dosage, and decrease the drug distribution in nontarget tissues, thereby reducing the toxicity and side effects [5]. After administration through the lung, the drugs can be transported into the systemic circulation through the thin alveolar epithelial cell layer. Thus, PDDS can also be used for systemic drug delivery. Due to the large absorption area of the lung and the lack of degrading enzymes, pulmonary administration can be used as a convenient and effective noninjection administration method for biomacromolecular drugs, such as proteins and nucleic acids [6–8]. The PDDS can maintain local drug concentration, reduce systemic side effects, control drug release, promote drug absorption, prolong the drug action time, and improve patient compliance. Therefore, PDDS has become a hotspot to prevent and treat diseases in current research [9, 10].

from the right ventricle will pass through the lung, which is up to 5 L per minute. This blood flow volume is the equivalent of the total blood flow in all other organs and tissues of the body [16]. Besides, the chemical and enzymatic degradation activity in the lung is relatively low, which can reduce the hydrolysis of the bioactive macromolecules, such as proteins, peptides, and nucleic acids. Thus, these drugs can maintain a good biological activity after pulmonary administration,

In summary, the huge absorption area, abundant capillaries, and minimal transport distance together contribute to the rapid absorption of pulmonary administration. After being quickly absorbed in the lung, the drugs will directly enter the systemic blood circulation, avoiding the first-pass effect of the liver, which is beneficial to improve the bioavailability of the drugs. And due to the low enzyme activity in the lung, the drug's adverse reactions during local administration can be reduced, which is especially suitable for the patients who need long-term adminis-

2.2 The characteristic and development of pulmonary administration

Pulmonary administration has been initially used to relax the tracheal smooth muscles to treat the acute exacerbation of asthma, and the disease is treated by inhaling the drugs through the trachea and the lung in the forms of drug aerosol particles or dry powder particles [20]. In general, there are two therapeutic purposes for pulmonary administration. One is the treatment of diseases in the lung, such as bronchial asthma and chronic obstructive pulmonary disease. The other purpose is to achieve systemic treatment through the pulmonary absorption of the drugs. Pulmonary inhalation administration can deliver the therapeutic agents directly to the lesion site, which can reduce the drug distribution in nontarget tissues. Therefore, for the treatment of pulmonary diseases, inhalation administration has a higher therapeutic index and fewer side effects than oral administration. And pulmonary inhalation is the preferred administration method for bronchodila-

With the deep understanding of lung functions and lung diseases in medicine field, pulmonary inhalation is recognized as a simple and effective administration route for the respiratory tract and other disease treatments. The types of the pulmonary inhalation-treated diseases have been gradually increasing, such as the insulin aerosol for treating diabetes, and the salmon calcitonin powder for the treatment of osteoporosis and osteoarthritis [22]. In recent years, the number of studies on pulmonary inhalation of macromolecular drugs, such as proteins and peptides, has been increasing. These macromolecular drugs (such as insulin, growth hormone, vaccines, and cytokines) can be formulated into pulmonary administration preparations for local or systemic treatment. However, most of the pulmonary inhalation drugs currently used in clinical treatment is short-acting preparations, which require frequent administrations (about 3–4 times a day). Therefore, the long-acting preparations should be developed, because they can maintain stable blood concentrations and also increase the compliance of the patients [23]. At the same time, the sustained or controlled drug release preparations for pulmonary administration can effectively regulate drug release behavior and promote drug absorption rate, thereby contribut-

The particle size of the pulmonary inhalation preparations directly affects the deposition form and deposition site in the lung [24–26]. The particles of sizes >5.0 μm produce inertial impact and are deposited in the pharynx, larynx, and upper respiratory tract. Particles of sizes 1.0–5.0 μm mainly reach the deep part of the respiratory tract, trachea, bronchi, and alveolar surface by gravity deposition.

which will be beneficial to improve the drug bioavailability.

Applications of Chitosan in Pulmonary Drug Delivery DOI: http://dx.doi.org/10.5772/intechopen.87932

tors, β2-receptor agonists and corticosteroids [21].

ing to the achievement of ideal therapeutic effects [10].

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tration of the medicine [17–19].

Chitosan (CS) is a natural and widely available polycationic polysaccharide, and it has many unique physicochemical properties, good biocompatibility, and satisfactory biodegradability [11]. CS has been a popular biomaterial in pharmaceutical research for decades and is widely used in drug delivery [12]. As a drug carrier, CS can control drug release and improve the dissolution of poorly soluble drugs. A large number of studies have reported the developments and applications of CS-based materials as drug delivery carriers with versatile functions, such as CS-based beads, films, sponges, hydrogels, microspheres, and nanoparticles (NPs) [13]. Moreover, CS contains a large number of positively charged amino groups. These positive charges can interact strongly with the negatively charged mucosa membranes and adsorb on the mucosal surface, thereby avoiding the drugs being removed by the cilia, improving the adhesion rate, reducing drug clearance, and providing conditions for the drugs to penetrate through the cell membrane. At the same time, studies have shown that CS can open the tight junctions between the cells, which will promote drug transportation through the epithelial tissues, and increase the drug absorption rate and bioavailability [14]. Thus, CS is a suitable material especially for PDDS.

In this chapter, we focus on the applications of CS in pulmonary drug delivery. The research progress of PDDS and the applications of CS in PDDS are reviewed, and many representative and advanced studies on CS-based PDDS are enumerated in detail.
