Novel lipid-based hollow-porous microparticles as a platform for immunoglobulin delivery to the respiratory tract.
OBJECTIVE
Delivery of specific antibodies or immunoglobulin constructs to the respiratory tract may be useful for prophylaxis or active treatment of local or systemic disorders. Therefore, we evaluated the utility of lipid-based hollow-porous microparticles (PulmoSpheres) as a potential delivery vehicle for immunoglobulins.


METHODS
Lipid-based 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) bioavailability subsequent to nonaqueous liquid instillation into the respiratory tract of BALB/c mice, using ELISA and Western blotting; iii) bioactivity in terms of murine immune response to xenotypic epitopes on human IgG, using ELISA and T cell assays; and iv) mechanisms responsible for the observed enhancement 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, although 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 xenotypic epitopes and was associated with receptor-mediated loading of alveolar macrophages.


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.
Bot
A I
AI
Department of Exploratory Biological Research, Alliance Pharmaceutical Corp, San Diego, California, USA. axb@allp.com
Tarara
T E
TE
Smith
D J
DJ
Bot
S R
SR
Woods
C M
CM
Weers
J G
JG
D000280:Administration, Inhalation; D000336:Aerosols; D000818:Animals; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000276:immunology; D005260:Female; D005456:Fluorescent Dyes; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000494:pharmacology; D006801:Humans; D007074:Immunoglobulin G / Q000276:immunology / Q000494:pharmacology*; D008055:Lipids / Q000493:pharmacokinetics*; D008168:Lung / Q000276:immunology* / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008863:Microspheres; D010316:Particle Size; D010446:Peptide Fragments / Q000276:immunology / Q000493:pharmacokinetics; D051381:Rats; D017207:Rats, Sprague-Dawley
D000336:Aerosols; D000939:Epitopes; D005456:Fluorescent Dyes; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007074:Immunoglobulin G; D008055:Lipids; D010446:Peptide Fragments