Chitosan Structure and Main Characteristics

Chitosan-based particles loaded with proteins can be obtained by both physical and chemical methods. However, the chemical crosslinking methods use toxic organic solvents (to make water/oil emulsions), heat, vigorous agitation or chemicals that might compromise the stability and biocompatibility of the proteins [93]. 

A technique used to obtain spherical particles is the spray-drying technique. The spray-drying method has reportedly provided small-size, protein-loaded chitosan-alginate microparticles with appropriate protein immobilization capacity [98]. It has been applied to BSA/sodium alginate/chitosan solutions to obtain microparticles [98]. Moreover, chitosan nanoparticles can be obtained by ionic crosslinking method. It has produced nanoparticles based on ionic gelation process of tripolyphosphate (TPP) and chitosan [99]. Nevertheless, another physical method called layer-by-layer can be used to form chitosan particles. Through the layer-by-layer technique submicron (40 nm) capsules with poly(L-aspartic acid) and chitosan for transmucosal delivery of proteins and peptides have been obtained [100]. 

Peptides and proteins are generally administered by the parenteral route. However, complications such as thrombophlebitis or tissue necrosis and poor patient compliance have stimulated the investigation of alternative nonparenteral routes [101]. 

The oral administration of peptidic drugs requires their protection from degradation in the gastric environment and the improvement of their absorption in the intestinal tract. In general, the barriers can be divided into the absorption and the enzymatic barrier, which are mainly responsible for a very low bioavailability of orally given peptides and proteins. Because of i) their permeation enhancing effect, ii) enzyme inhibitory capabilities, and iii) mucoadhesive properties, chitosan and 

Currently, there are still limited, incomplete, and insignificant human studies about the biocompatibility and biodegradability of newly developed chitosan derivatives. There are limited studies published in peer-reviewed journals describing the biocompatibility of chitosan or its derivatives, due to an absence of interest from manufacturers in applications of chitosan or its derivatives in the design of medical devices [104]. 

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