Compositions and methods for enhanced transepithelial and transendothelial transport or active agents

• US 5,254,342 A
• Filed: 09/30/1991
• Issued: 10/19/1993
• Est. Priority Date: 09/30/1991
• Status: Expired due to Fees

• Current Assignee: University of Southern California
• Original Assignee: University of Southern California
• Inventors: Wan, Jiansheng, Shen, Wei-Chiang
• Primary Examiner(s): Page, Thurman K.
• Assistant Examiner(s): AZPURU, CARLOS A
• Application Number:
  US07/768,508
• Time in Patent Office: 750 Days
• Field of Search: 424/401, 424/447, 435/240.1, 435/240.2, 435/240.3, 435/240.31
• US Class Current: 424/401
• CPC Class Codes: A61K 47/644 Transferrin, e.g. a lactoferrin or ovotransferrin

Abstract

Compositions and methods for use in enhancement of transmembrane and transcellular transport of an active agent, in particular a peptide or protein, in which at least one carrier for transmembrane or transcellular transport of an active agent which is a ligand for a cell-surface receptor is used to form a ligand/active agent conjugate and at least one transfer enhancement agent which enhances transcytosis of the resultant cell-surface receptor/ligand complex is administered to accelerate transcytosis. As an example, the effects of brefeldin A and monensin on transferrin (Tf) transcellular transport, Tf receptor (TfR) distribution and TfR-mediated endocytosis in filter-grown MDCK cells are described. The transfer enhancement agents markedly enhanced the transcytosis of ligand/active agent complexes in both the apical-to-basal and the basal-to-apical directions, but did not increase the transcytosis of agents which were not bound to a cell-surface receptor ligand as carrier. Furthermore, this enhanced transcytosis was abolished by competition with excess unlabeled Tf, confirming that it was a TfR-mediated process.

Claims

1. A method for enhancing transcellular or transmembrane transport of an active agent, said method comprising:

forming a conjugate of said active agent with a cell-surface receptor ligand for a transferrin receptor; and

administering said conjugate and a transfer enhancing amount of a transfer enhancement agent which enhances transcytosis of a cell-surface receptor/ligand complex.

2. A method according to claim 1, wherein said transfer enhancement agent is brefeldin A or monensin.