ABSTRACT

Inhalation drug delivery is an attractive approach because it is less invasive than other treatment methods. For treating respiratory diseases, inhalation allows direct accessibility to target cells, e.g., β-agonist inhalation for the treatment of asthma. This approach is also appealing for systemic drug delivery because the lungs have a large epithelial surface area, which permits high drug permeability, and low drug-metabolizing activity than other administration routes such as the gastrointestinal tracts (Patton and Byron 2007). The inhaled insulin product Exubera is one of the most successful examples of systemic drug delivery. However, the clinical application of inhalation drug delivery remains limited. A major problem associated with conventional inhalation therapy is the rapid clearance of drugs from lung tissues, necessitating repetitive administration to obtain a sustained therapeutic effect. One promising solution to inhibit rapid clearance is increasing the molecular size of the drug by encapsulating it into functional particles. Nanoparticles (NPs) with the size of several tens of nanometers are effective for this purpose because they are advantageous for efcient cellular uptake by endocytosis, wide distribution, and improved tissue retention (Azarmi et al. 2008; Rytting et al. 2008; Bailey and Berkland 2009). Indeed,

CONTENTS

14.1 Basic Design of a Polyplex Nanomicelle for Inhalation Delivery ...............................225 14.1.1 NP-Based Drug Delivery to the Lungs and Polyplex Nanomicelle

Application ..............................................................................................................225 14.1.2 Gene Delivery into the Lungs and Application of Polyplex Nanomicelles ...227