Development of nanoparticle based delivery systems for sublingual immunotherapy

The prevalence of IgE mediated allergic diseases is increasing dramatically in industrialized countries. Sublingual immunotherapy (SLIT) has been demonstrated to be a safe and efficacious treatment for IgE mediated allergic diseases, but requires protracted treatment duration. Even though SLIT is considered to have a better safety profile than subcutaneous immunotherapy, SLIT can still cause adverse events requiring clinical supervision for the first administration.

Optimization of SLIT, by reducing the administration dose and treatment duration, would improve safety profile. For this purpose, development of nanoparticle delivery systems that can carry antigen across oral mucosa and improve targeting of antigen to the oral immune system would be favourable. This thesis presents seven delivery systems, including liposomes (neutral and cationic) and acylated peptide, which were tested in an ovalbumin (OVA)-induced allergic airway inflammation model for their ability to improve immune tolerance induction of ovalbumin (protein and peptide) when delivered sublingually.

In the liposome study, mice were treated sublingually during two weeks with free or liposome encapsulated OVA (OVA-liposomes) followed by intraperitoneal injections and intranasal challenge. Mice treated sublingually with OVA-liposomes showed a significant reduction of airway eosinophilia, OVA-specific IgE antibodies and splenocyte proliferation in comparison to free OVA.

In addition, reduced levels of IFN-ɣ and IL-5 were observed in spleen cell supernatants from OVA-liposome treated mice compared to the sham-treated group. A non-significant reduction of IL-4 and IL-10 in comparison to the sham-treated group was seen. In the study with acylated peptide, mice were SLIT treated with free or acylated OVA323-339 peptide during two weeks followed by intraperitoneal injection.

Mice treated with acylated OVA323-339 showed a non-significant tendency of downregulating the proliferation of spleen cells compared to free OVA323-339. The same down-regulating tendency was seen for IFN- ɣ, IL-4, IL-5 and IL-10.