Sublingual immunotherapy (SLIT) is a non-invasive and efficacious treatment of type I respiratory allergies (Canonica & Passalacqua Allergy 2006; 61:20-23, Wilson et al. Allergy 2005; 60:4-12). However, it remains to be optimized, with respect for example to treatment duration and administration schedules. In this context, appropriate delivery systems are to be identified to improve tolerance induction via the sublingual route. Mucoadhesive and/or particulate formulations appear to be particularly promising with the aim of (i) enhancing contact duration with the mucosa, thus improving the amount of allergen penetrating the sublingual mucosa, and (ii) targeting antigen-presenting cells (APCs) within the oral mucosa, which are prone to induce tolerance (Moingeon et al. Allergy 2006; 61:151-165, Novak & Bieber J Allergy Clin Immunol 2008; 121:S370-4).
Chitosan is a polycationic polysaccharide derived by deacetylation of chitin. Chitosan naturally occurs in crustaceans, insects, mushrooms and microorganisms. It is biodegradable, biocompatible, well tolerated and shows no irritating or sensitizing properties, consequently it has been approved by the FDA for human utilization (Jayakumar et al. Int J Bio Macromolecules 2007; 40:175-181).
Chitosan-based products are already in use in the medical, cosmetic, health supplement and environmental industries. Most particularly, among the possible forms of chitosan-based polymers, chitosan particles are interesting delivery system candidates to target the antigen to mucosal DCs because of their polycationic nature, which is responsible for their mucoadhesiveness, and because of their particulate form, which facilitates uptake by APCs and transport to secondary lymphoid organs (O'Hagan & Valiante Nat Rev Drug Discov 2003; 2:727-735). In the field of antigen-specific tolerance induction, a few studies have investigated the effect of chitosan particles, mostly as a gene delivery system via the intranasal or oral route (Roy et al. Nat Med 1999; 5:387-391; Kumar et al. Genet Vaccines Ther 2003; 1:3; Chew et al. Vaccine 2003; 21:2720-2729)). As regards peptide delivery using chitosan, no sound teachings can be derived from prior art concerning the potential of chitosan as a delivery system. Thus, Porporatto et al. Int Immunol 2004; 16:433-441 report that the oral administration of low molecular weight chitosan in association with type II collagen promotes an anti-inflammatory environment early after feeding. Hall et al. J. Allergy Clin Immunol 2002; 100:883-89 show that intranasal administration of chitosan in association with an allergen reduces airway inflammation. Conversely, Cunningham et al. World Allergy Congress 2007 116, (Abstr) indicate that sublingual administration of an allergen in association with chitosan leads to a non-specific reduction of lung inflammation, which is not superior to the one observed when the allergen is administered alone.