Peptide-mediated intravesical delivery of therapeutic and diagnostic agents

Abstract

The present invention relates to compositions comprising therapeutic and / or diagnostic anionic agents together with cationic peptides and their use in methods for delivering the anionic agents to bladder cells.

Description

PRIORITY CLAIM[0001]This application is a division of U.S. patent application Ser. No. 14 / 846,536, filed Sep. 4, 2015, which claims priority to U.S. Provisional Application No. 62 / 046,585 filed Sep. 5, 2014, the contents of which are hereby incorporated by reference in its entirety herein.GRANT INFORMATION[0002]This invention was made with government support under Grant No. DK088836 awarded by the National Institutes of Health. The government has certain rights in the invention.INTRODUCTION[0003]The present invention relates to methods and compositions for administering agents to cells in the bladder, whereby a cationic peptide or a mixture of cationic peptides is used to deliver an anionic therapeutic or diagnostic agent.BACKGROUND OF THE INVENTION[0004]Introduction of short strands of antisense DNA with sequences complementary to the mRNA encoding a particular protein inside the cell is being explored as a therapeutic approach [1]. The inserted antisense oligonucleotide (“ODN”) bi...

AI Technical Summary

Benefits of technology

The invention is about using a combination of therapeutic and diagnostic agents with cationic peptides to treat and diagnose bladder cells. The cationic peptides act as carriers for the anionic agents, helping them enter bladder cells. This technique has been tested in animals and is being developed for use in humans. The technical effect is that cationic peptides improve the delivery of therapeutic agents to target cells.

Problems solved by technology

However, applied research for bladder diseases has lagged behind other disciplines.

Drug development of this approach has been hampered by inefficient cellular uptake of the ODN.

It is known that tight junctions in urothelium are compromised in cancerous condition [6] and therefore the strategy of relying on concentration gradient may not work in non-cancerous diseased condition where the barrier is intact, such as in overactive bladder.

Several approaches have been tried to increase the bladder uptake of ODN without compromising the bladder barrier, but all have limitations.

The translation of basic antisense research into therapeutics is also impeded by intracellular stability of ODN and potential for “off-target” gene silencing, immunostimulation, and other side effects.

A significant limitation for medicine, particularly treatments given by the intravesical route (via a catheter into the bladder), is the poor permeability of the bladder to outside agents.

Efficient cellular uptake of many chemical agents is still a challenge.

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