Targeted delivery of antimicrobial agents

Abstract

A cationic antimicrobial peptide (CAMP) conjugate is disclosed. The CAMP conjugate may be made by identifying a suitable carrier peptide; identifying a suitable antimicrobial agent; creating a conjugate by conjugating the peptide with the antimicrobial agent; and evaluating and refining the conjugate. The peptide may be short peptide based on the sequence of a CAMP, such as human β-defensin-3. The peptide can be directly connected to the antimicrobial agent or through a linker segment. The antimicrobial agent may be connected to the peptide or the linker segment through stable or cleavable bonding. The peptide may carry and facilitate the delivery of the conjugated antimicrobial agent to a microbe.

Description

CROSS REFERENCE TO RELATED APPLICATIONS[0001]The present application is a continuation of U.S. application Ser. No. 12 / 502,420, filed Jul. 14, 2009, which claims the benefit of Provisional Patent Application Ser. No. 61 / 081,557, filed on Jul. 17, 2008, both of which are hereby incorporated by reference.BACKGROUND OF THE INVENTION[0002]Before the discovery of antibiotics, community-acquired infections were a major threat to the health and welfare of people in the United States, and they continue to be a major problem in developing countries. However, soon after the discovery of penicillin and wide spread access to antibiotics in the 1940's, bacteria began to develop varied degrees of resistance to these drugs. While new drugs have been introduced since the discovery of penicillin, the majority of them are the result of varied combinations of substituents on one of about 9 molecular scaffolds. There should be no surprise that the number of microbes developing resistance is growing rap...

AI Technical Summary

Benefits of technology

The patent text discusses the problem of antibiotic resistance and the need for new treatments for gastrointestinal infections, particularly in children in developing nations. The text describes various strategies for targeted delivery of antimicrobial agents to bacteria, but there is still a need for effective treatments that can address the threat of antibiotic resistance. The technical effect of the patent text is to provide new methods for developing therapeutics that can effectively treat gastrointestinal infections caused by resistant bacteria.

Problems solved by technology

Before the discovery of antibiotics, community-acquired infections were a major threat to the health and welfare of people in the United States, and they continue to be a major problem in developing countries.

For example, antibiotic resistance was initially a problem associated with nosocomial infections.

Antibiotic resistance appears to now threaten the utility of “last resort” drugs, such as vancomycin, the drug of choice for treating methicilin- and multidrug-resistant Staphylococcus aureus infections.

The problem of antibiotic resistance is farther complicated by the threat of bioterrorism, and the potential use of pathogens that have been intentionally altered in order to enhance their resistance to antibiotics and to enhance their virulence or lethality.

Today, gastrointestinal pathogens continue to present a threat to the health of Americans and people worldwide, particularly children in developing nations.

While many of these illnesses can be treated, several of them (such as shigellosis and cholera) can have fatal consequences if untreated.

Shigellosis is a greater problem in developing countries, accounting for about 99% of the estimated 165 million cases worldwide each year.

However, many compounds that show very potent antimicrobial activity tend not to be suitable for use as therapeutics due to undesirable side effects or poor selective toxicity.

Yet, if delivered nonspecifically, undesirable side-effects may result.

Furthermore, while a diverse range of strategies for targeted delivery of therapeutics have been explored for the selective delivery of chemotherapeutics to cancerous cells, they have only recently been investigated for the treatment of infectious disease.

In these studies, cells were treated with the conjugate and then exposed to 660 nm light, which triggers the generation of singlet oxygen and free radicals leading to cell death.

While useful in localized applications, polylysine conjugates are generally not well suited for systemic administration.

They tend to provide limited specificity in their delivery of attached drug moieties by entering host cells, as well as invading microbes.

However, at the same time, their specificity may also prevent their utility with organisms other than the one for which they were designed.

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