Pulmonary administration of therapeutic proteins using an immunoglobulin transport pathway

被引：69

作者：

Bitonti, Alan J. ^{[1
]}

Dumont, Jennifer A. ^{[1
]}

机构：

[1] Syntonix Pharmaceut, Waltham, MA 02451 USA

来源：

ADVANCED DRUG DELIVERY REVIEWS | 2006年 / 58卷 / 9-10期

关键词：

FcRn; transepithelial transport; erythropoietin; interferon alpha; interferon beta; follicle stimulating hormone; aerosol; Fc-fusion; protein; neonatal Fc receptor; lung;

D O I：

10.1016/j.addr.2006.07.015

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

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. (c) 2006 Elsevier B.V All rights reserved.

引用

页码：1106 / 1118

页数：13

共 62 条

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