Conjugates of membrane translocating agents and pharmaceutically active agents

Abstract

Membrane translocation peptides, compositions comprising them, chimeric molecules comprising them, and methods of using them to achieve transmembrane transport of various agents.

Description

CROSS REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of application Ser. No. 09 / 671,089 filed Sep. 27, 2000, incorporated by reference herein in its entirety, and also claims the benefit of U.S. provisional application Ser. No. ______ filed Apr. 30, 2001 with the title “Lipid-Comprising Drug Delivery Complexes and Method for Their Production”, incorporated herein in its entirety.FIELD OF THE INVENTION [0002] The present invention relates to peptides, which enhance uptake of a pharmaceutically active agent into a cell, into or out of an intracellular compartment, and across a cell layer. More particularly, the present invention relates to membrane translocating peptides, thereof and to the nucleotide sequences coding therefor, which enhance uptake of a pharmaceutically active agent into a cell, into or out of an intracellular compartment, and across a cell layer either directly or from a pharmaceutically active agent loaded particle. BACKGROUND OF...

AI Technical Summary

Benefits of technology

[0057] MTLPs, MTLP-active agent complexes and MTLP-active particle complexes can be used alone, in combination with or conjugated to other molecules including, but not limited to, molecules that bind to target pathways, to nuclear uptake pathways and to endosomal pathways, molecules that enable mucoadhesion, molecules that facilitate diffusion across lipid membranes or through water filled pores and molecules that regulate or direct intra-cellular trafficking. That is, by using different mechanisms simultaneously, active agent bioavailability may be enhanced.

[0088] Another aspect of the present invention is a method to provide a method for preventing a pathological disorder by oral administration of a a translocating peptide-active particle complex, wherein the active particle contains a prophylactic agent, such that the systemic concentration of the prophylactic agent is effective to prevent the pathological disorder.

Problems solved by technology

However, these studies do not address the use of membrane translocating peptides to enhance active agent uptake into a cell into and out of an intracellular compartment, or across a cell layer when the active agent is complexed to a membrane translocating peptide or when the active agent is incorporated into a particle and the particle is modified with (hereinafter, “complexed to”) a membrane translocating peptide.

Intravenous administration can result in adverse effects from rapid accumulation of high concentrations of drug, in patient discomfort and in infection at the injection site.

Intramuscular administration can cause pain at the injection site.

Subcutaneous administration is not suitable for large volumes or for irritating substances.

Although oral administration is the preferred route, many active agents are not absorbed efficiently across the GIT epithelium.

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