Biomimetic particles and films for pathogen capture and other uses

Abstract

The identification and immobilization of glycosylated molecules having biomimetic properties, more particularly naturally-occurring, tissue-derived, non-immunological glycan sequences or functional equivalents thereof, on solid state surfaces and films or on membranes arising at the interface between non-polar and polar materials is described herein. The biomimetic glycosylated films and particles constructed therefrom have industrial, environmental, diagnostic and / or therapeutic utility in the binding, capture, and / or extraction of pathogens, toxins and / or contaminants, in vivo, in vitro or in situ. The present invention further extends to the use of such biomimetic films and particles for the delivery of other therapeutic molecules as well as in the construction of body contacting devices having enhanced biocompatibility and reduced immunogenicity.

Description

PRIORITY[0001]This application claims the benefit of U.S. Utility patent application Ser. No. 11 / 761,045 filed Jun. 11, 2007, referred to hereinafter as the '045 Application, the contents of which are incorporated by reference herein in its entirety. This application further claims the benefit of U.S. Provisional Patent Application Nos. 61 / 027,375 filed Feb. 8, 2008 and 61 / 044,710 filed Apr. 14, 2008, referred to hereinafter as the '375 and '710 applications respectively, the entire contents of which are incorporated herein by reference.FIELD OF THE INVENTION[0002]The present invention relates generally to the field of glycomics and the identification and immobilization of glycosylated molecules having biomimetic properties, more particularly naturally-occurring, tissue-derived, non-immunological glycan sequences or functional equivalents thereof, on solid state surfaces and films or on membranes arising at the interface between non-polar and polar materials. The present invention a...

AI Technical Summary

Benefits of technology

The present invention provides novel biomimetic films and particles that can be used for pathogen capture and other applications. These films and particles have biomimetic properties and can be made by immobilizing glycosylated molecules onto a solid substrate. The glycans or glycan sequences on the surface of cells, particularly epithelial cells, represent the principal binding sites for pathogens at the initiation of a host-tropism type infection. The biomimetic films and particles can be used for diagnostic, therapeutic, or other purposes. The invention also provides methods for making and using the biomimetic films and particles.

Problems solved by technology

However, these techniques are limited in their ability to capture unexpected, uncharacterized, rapidly evolving or engineered pathogens.

While many of these microorganisms are symbiotic in nature, others are pathogenic.

However, this option is often unacceptable when dealing with infection in the very young, the very old, in individuals whose immune system is impaired or compromised or when dealing with particularly virulent strains against which the body may not be able to mount an adequate defense.

However, antibiotic therapy has its limitations.

For example, antibiotics are ineffective against viral pathogens as well as the growing number of antibiotic resistant strains, the onset of which many scientists link to the overuse of antibiotics.

In addition, antibiotics are not always readily available, particularly in economically disadvantaged locations in the world.

Moreover, antibiotic therapy is not always advisable, even in the treatment of bacterial infections.

Studies have shown that 5-10% of individuals infected by STEC will develop hemolytic-uremic syndrome (HUS), and, of those, half will have renal damage and one in ten will die or have renal failure.1 However, in vivo treatment of shiga toxin-producing bacteria using antibiotics can be dangerous because the bacteria have been shown to produce more toxin when stressed.23 1 Cheleste M Thorpe, Shiga toxin-producing Escherichia coli infection, Clin Infect Dis. 2004 May 1; 38 (9):1298-3032 Wong, C, M. D., et al.

Accordingly, since antibiotics are not always advisable, available or even effective, alternative therapeutic treatments for pathogenic infections are heartily sought.

This later method, also known to those skilled in the art, is less efficient in the expression of active moieties at the surface since the molecules of interest may be embedded in a manner where the active moieties are not exposed at the surface.

In both these situations, when the polar solvent is removed, the electrical forces which maintain the alignment of the amphiphilic compounds are also removed and the membrane structure fails.

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