Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway

• Published in: Advanced drug delivery reviews Vol. 58; no. 9; pp. 1106 - 1118
• Main Authors: Bitonti, Alan J., Dumont, Jennifer A.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 31.10.2006
• Subjects: Administration, Inhalation; Aerosol; Animals; Drug Delivery Systems - methods; Erythropoietin; Fc-fusion protein; FcRn; Follicle stimulating hormone; Humans; Immunoglobulin Fc Fragments - administration & dosage; Interferon alpha; Interferon beta; Lung; Lung - metabolism; Neonatal Fc receptor; Pharmaceutical Preparations - administration & dosage; Receptors, Fc - metabolism; Recombinant Fusion Proteins - administration & dosage; Transepithelial transport; Erythropoietin; Fc-fusion protein; Aerosol; Lung; Interferon alpha; Interferon beta; FcRn; Neonatal Fc receptor; Transepithelial transport; Follicle stimulating hormone
• ISSN: 0169-409X; 1872-8294
• DOI: 10.1016/j.addr.2006.07.015

We have applied a “physiologic” approach to the pulmonary delivery of therapeutic proteins, utilizing an immunoglobulin (antibody) transport pathway recently shown to be present predominantly in the conducting airways of the human respiratory tract. Therapeutic proteins are fused to the Fc-domain of an IgG1, allowing them to bind with high affinity to the antibody transport receptor, FcRn. Liquid aerosols are administered into the lung using normal breathing maneuvers and efficient delivery of several different Fc-fusion proteins has been achieved with retention of biological activity and an increase in circulating half-life. A new paradigm for the pulmonary delivery of therapeutic proteins and a fundamental advance in the construction of Fc-fusion proteins for this purpose will be described.