Chitosan hydrochloride

Eudragit RS microspheres containing chitosan hydrochloride were prepared by the solvent evaporation method using an acetone/liquid paraffin solvent system, and their properties were compared with Eudragit RS microspheres without chitosan. The content of pipemidic acid, an antibacterial, increased in larger microspheres as a consequence of cumulation of undissolved pipemidic acid particles in larger droplets. Pipemidic acid release was faster from microspheres with chitosan [212]. 

The ability of chitosan hydrochloride to enhance the transcorneal permeability of the drug has been demonstrated [289]. Polyethylene oxide (PEO) was used as a base material to which ofloxacin-containing chitosan microspheres prepared by spray-drying were added and powder compressed resulting in circular inserts (6 mm). 

Cationic chitosan derivatives, such as /Y-trimethyl chitosan chloride, increase the paracellular delivery of macromolecules due to the interaction between the positive charges of chitosan and anionic glycoproteins on the surface of the enterocytes. Other chitosans, e.g., chitosan hydrochloride, were reported to shift specific cations required for the efficient closing of tight junctions [21] or reorganize the protein structure of tight junctions [22]. This topic is reviewed in a separate chapter of this book (Chapter 3). 

FIGURE 3.1 Chemical structures of chitosan, iV-trimethyl chitosan hydrochloride, and chitosan-TBA conjugate. 

FIGURE 3.3 Effect of TMC-H, TMC-L, and chitosan hydrochloride on the permeability of [14C] mannitol across Caco-2 cell monolayers. The results are expressed as the mean + SD (n = 3). 

Rossi, S., et al. 2001. Characterization of chitosan hydrochloride-mucin rheological interaction Influence of polymer concentration and polymer mucin weight ratio. Eur J Pharm Sci 12 479. 

Rossi, S., Ferrari, F. Bonferoni, M.C. and Caramella, C. (2000) Characterization of chitosan hydrochloride-mucin interactions by means of viscosimetric and turbidimetric measurements. Eur. J. Pharm. Sci. 10 251-257. 

Sieval, A.B., Thanou, M, Kotze, A.F., Verhoef, J.C., Brussee, J. and Junginger, H.E. (1998) Preparation and NMR-characterization of highly substituted A-trimethyl chitosan hydrochloride. Carbohydr. Polym 36 157-165. 

Boucard et al. [184] prepared bilayered physical hydrogels for the treatment of fullthickness bum injuries in a pig model. The upper rigid protective layer is generated from a solution of chitosan hydrochloride in hydroalcoholic medium and is designed to provide suitable mechanical properties and ensure gas exchange. The lower layer is soft and flexible, which can fill the shape of the wound and ensure... 

The chitosan and its derivatives show no acute toxicity and are not absorbed via transdermal route. The European pharmacopoeia contains a single monograph on chitosan hydrochloride. In the United States, chitosan is currently being included in the US Pharmacopoeia [Sarmento and das Neves, 2012]. The chitosan and its derivatives are deemed safe for use as permeation enhancer for transmucosal delivery of hydrophilic drugs and offer promising prospects for novel pharmaceutical applications [Junginger and Verhoef, 1998]. Despite the chitosan and its derivatives interact with lipids and proteins of the membranes of stratum corneum, they may not penetrate into deeper layers of the skin. This can be inferred from the absence of skin irritation by chitosan and its derivatives in Draize test [Aoyagi et al., 1991]. 

The interaction of chitosan with carboxylic polyacids leads to the formation of an insoluble PEC. Chitosan is insoluble in neutral and basic media, therefore the stoichiometric PEC is usually obtained by mixing equimolar quantities of the polyacid and chitosan hydrochloride. The complex is formed according to the following reaction ... 

Gamzazade A.I., Nasibov S.M., Formation and properties of polyelectrolyte complexes of chitosan hydrochloride and sodium dextransulfate, Carbohyd. Polyrru, 50(4), 2002, 339-343. 

Signini, R. and S. P. Campana-Fitho. 1999. On the preparation and characterization of chitosan hydrochloride. Polym. Bull. 42(2) 159-166. 

Seyfarth, R, Schliemann, S., Eisner, P. et al. 2008. Antifungal effects of low-molecular-weight chitosan hydrochloride, carboxymethyl chitosan, chitosan oligosaccharide andiV-acetyl-D-glucosamine against Candida albicans, Candida krusei and Candida glabrate. International Journal of Pharmaceutics 353 139-148. 

Ferrari F, Rossi S, Cristina B, Carmella C. Characterization of rheological and mucoadhesive properties of three grades of chitosan hydrochloride. Farmco 1997 52 493-497. 

Other derivatives and chitosan salts, such as chitosan lactate, chitosan aspartate, chitosan glutamate, and chitosan hydrochloride, were also shown to be good candidates for nasal sustained release of, for example, the antibiotic vancomycin hydrochloride [87]. In addition, chitosan microparticles with diphtheria toxoid (DT) for nasal administration were produced. These microparticles administration resulted in a protective systemic and local immune response against DT with enhanced IgG production. The induction of serum IgG responses were similar to secretory IgA levels, and are superior to parenteral administration of the vaccine [88]. 

Reference data on common chitosan salts are useful to assess the characteristics of complexes made by modified chitosans and DNA. Complexes formulated with several chitosan salts were assessed for complexing ability toward DNA, transfection efficiency in Chinese hamster ovary cells, and their effect on cell viability. Chitosan hydrochloride, lactate, acetate, aspartate and glutamate (chitosan MW 45 kDa) formed complexes with pcDNA3-CMV-Luc. Gel electrophoresis documented that complexes formed at N/P ratios above 2 with all chitosan salts. The transfection efficiency depended on the anion, on the chitosan MW, and on the N/P ratio maximum transfection efficiencies were at N/P ratio of 12, 12, 8, 6 and 6 for said salts, respectively. The MTT assay indicated that all chitosan/DNA complexes had low cytotoxicity (Weecharangsan et al., 2008). 

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