The safety of chitosan has been recently and comprehensively reviewed by, among others, Baldrick42 and Kean and Thanou

The safety of chitosan has been recently and comprehensively reviewed by, among others, Baldrick42 and Kean and Thanou.43 In vivo, the stability of chitosan is affected by molecular weight, degree of de-acetylation, and chemical modification;43 nevertheless, it is generally accepted that chitosan is not degraded within the human being intestine and thus effectively functions as an inert soluble fiber which is excreted via faeces.44-46 The oral LD50 in mice is reported to be 16 g/kg, which is similar to that of sugar.46,47 The use of chitosan for pharmaceutical and medical applications requires highly purified GMP-grade material comprising carbohydrate containing little or no residual protein; chitosan-based products should comply with appropriate pharmacopoeial checks. evoke strong immunological reactions and confer protecting immunity following (enteral) norovirus challenge. This short article summarizes the totality of the meaningful information (including key unpublished data) assisting the development of chitosan-adjuvanted vaccines. (LT) in certain strains of mice (e.g., Balb/c and C57BL/6) apparently as a result of transit via the olfactory nerve; interestingly these adjuvants were not recognized in the brains of additional strains of mice (e.g., CD-1 and additional outbred strains) nor in rats, rabbits, Ibuprofen (Advil) and baboons.14-16 Second came concerns over use of an LT-based nasal influenza virus vaccine (Nasalflu, Berna Biotech) due to association with Bells palsy (facial nerve paralysis) which subsequently led to the product being withdrawn from the market.17,18 In view of these events, more comprehensive information within the safety of mucosal adjuvants is a prerequisite for development and there is an increasing need for route-specific adjuvants and vaccines.19 Archimedes Development Ltd (Archimedes) has developed a novel delivery technology based on chitosan (ChiSys?), which has been demonstrated to enhance the intranasal delivery of standard medicines as well as peptides and proteins.20,21 This technology has shown promise for the nose delivery of vaccine antigens, with the added benefit that chitosan Ibuprofen (Advil) displays positive adjuvant properties, having a potential for clinical benefit. With respect to the safety issues raised above, a substantial amount of preclinical and medical safety data has been generated on chitosan and its safe use for intranasal drug delivery and as a vaccine adjuvant has been widely reported in the Ibuprofen (Advil) literature.22-33 Chitosan: Chemical and Physicochemical Characteristics Chitosan, the common term for a family of linear polysaccharides which exist as copolymers of -(1-4)-linked glucosamine and N-acetylglucosamine, is usually commercially obtained by partial de-acetylation of -chitin produced from the exoskeletons of crustacea or the cell walls of fungi.34-36 The molecular weight, degree of de-acetylation Rabbit Polyclonal to Cortactin (phospho-Tyr466) (charge denseness) and distribution of acetyl groups strongly influence the physicochemical and biological properties of chitosan and directly affect its power.20,37,38 Natural chitosan salts tend to be largely insoluble above pH 6 which could be problematic for the delivery of vaccine antigens that are soluble and stable at neutral pH or above.6 Improved aqueous solubility of chitosan has been achieved by molecular changes largely associated with primary amine organizations although hydroxyl organizations have also been modified.6,20 In solution, amino groups of chitosan are protonated and the resultant soluble polysaccharide is definitely positively charged (cationic) conferring chitosan with mucoadhesive properties which are a critical component of its use for nasal drug and vaccine delivery applications.39,40 Security of Chitosan General safety of chitosan As described above, the term chitosan can symbolize a range of polymers individually characterized by their molecular weight, degree of de-acetylation and derivatisation, so published safety data need to be interpreted with some caution. However, chitosan is definitely widely regarded as a biocompatible, nontoxic, and non-allergenic material that is, consequently, highly suitable for use in medical and pharmaceutical applications.41 Chitosan salts, especially those derived from shellfish, have been tested for safety and toxicity in a number of Ibuprofen (Advil) animal species, and by numerous routes of administration.22,23 Kitozyme24 and Primex Corporations25,26 have compiled comprehensive info as part of self-certifications to support a generally recognized as safe (GRAS) status. The security of chitosan offers been recently and comprehensively examined by, among others, Baldrick42 and Kean and Thanou.43 In vivo, the stability of chitosan is definitely affected by molecular weight, degree of de-acetylation, and chemical modification;43 nevertheless, it is generally accepted that chitosan is not degraded within the human being intestine and thus effectively functions as an inert soluble fiber which is excreted via faeces.44-46 The oral LD50 in mice is reported to be 16 g/kg, which is similar to that.