**15. Biodegradability**

The claim "biodegradable" is often associated with environmentally friendly products. It is defined as being able to be broken down by natural processes, into more basic components. Products are usually broken down by bacteria, fungi or other simple organisms [82].

An important aspect in the use of polymers as drug delivery systems is their metabolic fate in the body or biodegradation. In the case of the systemic absorption of hydrophilic polymers such as chitosan, they should have a suitable Mw for renal clearance. If the administered polymer's size is larger than this, then the polymer should undergo degradation. Biodegradation (chemical or enzymatic) provides fragments suitable for renal clearance. Chemical degradation in this case refers to acid catalysed degradation i.e. in the stomach. Enzymatically, chitosan can be degraded by enzymes able to hydrolyse glucosamine–glucosamine, glucosamine–N- acetyl-glucosamine and N-acetyl-glucosamine– N-acetyl- glucosamine linkages [83]. Even though depolymerisation through oxidation– reduction reaction [84] and free radical degradation [85] of chitosan have been reported these are unlikely to play a significant role in the in vivo degradation.

Chitosan is thought to be degraded in vertebrates predominantly by lysozyme and by bacterial enzymes in the colon [83, 86]. However, eight human chitinases (in the glycoside hydrolase 18 family) have been identified, three of which have shown enzymatic activity [87]. A variety of microorganisms synthesises and/or degrades chitin, the biological precursor of chitosan. In general, chitinases in microorganisms hydrolyze N-acetyl-β-1,4 glucosaminide linkages randomly i.e. they are endo-chitinases (EC 3.2.1.14). Chitinases are also present in higher plants, even though they do not have chitin structural components.

Chemical characterisation assays determining the degradation of chitosan commonly use viscometry and/or gel permeation chromatography to evaluate a decrease in Mw [88]. Lysozyme has been found to efficiently degrade chitosan; 50% acetylated chitosan had 66% loss in viscosity after a 4 h incubation in vitro at pH 5.5 (0.1 M phosphate buffer, 0.2 M NaCl, 37 °C) [88]. This degradation appears to be dependent on the degree of acetylation with degradation of acetylated chitosan (more chitin like) showing the faster [89,90].

**Figure 5.** Biodegradation of chitosan thermosensible gel inside the rat´s body after 5 days.
