Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract

Purpose. Delivery of specific antibodies or immunoglobulin constructs to th e respiratory tract may be useful for prophylaxis or active treatment of lo cal or systemic disorders. Therefore, we evaluated the utility of lipid-bas ed hollow-porous microparticles (PulmoSpheres(TM)) as a potential delivery vehicle for immunoglobulins. Methods. Lipid-bared microparticles loaded with human immunoglobulin (hIgG) or control peptide were synthesized by spray drying and tested For: i) the kinetics of peptide/protein release, using ELISA and bioassays; ii) bioava ilability subsequent to nonaqueous liquid instillation into the respiratory tract of BALB/c mice, using ELISA and Western blotting; iii) bioactivity i n terms of murine immune response to xenotypic epitopes on human IgG, using ELISA and T cell assays; and iv) mechanisms responsible for the observed e nhancement of immune responses, using measurement of antibodies as well as tagged probes. Results. Human IgG and the control peptide were both readily released from the hollow-porous microspheres once added to an aqueous environment, althou gh the kinetics depended on the compound. Nonaqueous liquid instillation of hIgG formulated in PulmoSpheres into the upper and lower respiratory tract of BALB/c mice resulted in systemic biodistribution. The formulated human IgG triggered enhanced local and systemic immune responses against xenotypi c epitopes and was associated with receptor-mediated loading of alveolar ma crophages. Conclusions. Formulation of immunoglobulins in hollow-porous microparticles is compatible with local and systemic delivery via the respiratory mucosa and may be used as means to trigger or modulate immune responses.