ABSTRACT

A number of biomaterials have been incorporated in the development of nanoparticles that are used for the delivery of drugs and genes to cells and mammals, including humans. These include lipids and polymers such as poly(lactic-co-glycolic acid) (PLGA), polyethylene glycol (PEG), poly ethyleneimine (PEI), cyclodextrin, and chitosan. Of specific relevance to this review are the chitin-based cationic polymers, known as chitosan, which have been used historically as dietary supplements. The last decade has brought multiple advances in the use of chitosan nanoparticles, ranging from their use in drug delivery to the creation of theranostic particles, which are reviewed in this chapter in order to highlight their application in respiratory disease. 6.1.1 What Are Chitosan Nanoparticles?Chitosan (2-amino-2deoxy-(1→4)-β-d-glucopyranan) is a poly-aminosaccharide normally obtained by the alkaline deacetylation of chitin. It is the principal component of living organisms such as fungi and crustacea (Fig. 6.1). The degree of N-acetylation (DA) together with the molecular weight are the most important parameters in its characterization. The DA, which is by definition the molar fraction of N-acetylated units, is a structural parameter influencing charge density, crystallinity, and solubility, including the propensity to enzymatic degradation, with higher DAs leading to faster biodegradation rates. The major physicochemical properties of chitosan include the following: • Chitosan is a linear polymer of mainly anhydroglucosamine, which behaves as a linear polyelectrolyte at acidic pH. • Chitosan is nontoxic and bioabsorbable. • At pH below 6.5, chitosan in solution carries a high positive

charge density (one charge per glucosamine unit). • Since chitosan is one of the few cationic polyelectrolytes, it is an exception to the current industrial high molecular weight polysaccharides, which are mostly neutral or polyanionic. Chitosan has been sold as a dietary pill for decades. It has been shown to have extraordinary therapeutic properties, and chitosan nanoparticles have great potential to be a safe and effective carrier for genes and drugs.