The University of North Carolina at Chapel Hill

Novan, Inc.

Other

Kwangwoon University Industry-Academic Collaboration Foundation

Ligand Pharmaceuticals, Inc.

Mark H Schoenfisch

Nathan Stasko

Jae Ho Shin

Yuan Lu

Jian Bao

Lei Yang

Haibao Jin

Mona Jasmine R Ahonen

Dakota J Suchyta

Kaitlyn Rose Rouillard

Evan Scott Feura

Sara Elizabeth Maloney

Daniel Riccio

John Michael Ramsey

Katelyn P Reighard

William V Henley

Jonghae Youn

Evan M Hetrick

C Bryce Johnson

Robert J Soto

Maggie Malone-Povolny

Julia Nugent

Ben Privett

Benjamin Privett

Jae Ho Ho Shin

Provided here are nitric oxide-releasing compounds that include at least two different NO donor functional groups of the same class. In some embodiments, such nitric oxide-releasing compounds are macromolecules such as dendrimer and co-condensed silica. Pharmaceutical compositions, wound dressings, kits and methods of treatments are also provided herein.

Tunable nitric oxide-releasing macromolecules having multiple nitric oxide donor structures

Several embodiments of hyperbranched structures are disclosed. In some embodiments, the hyperbranched structures are covalently modified to store and release nitric oxide. Some embodiments pertain to methods of making and also to the use of hyperbranched structures. The covalently modified hyperbranched structures may be tailored to release nitric oxide in a controlled manner and are useful for eradication of both gram positive and gram negative bacteria as well as other microbes.

Nitric oxide-releasing hyperbranched compounds as antibacterial scaffolds and methods pertaining thereto

The subject matter disclosed herein is directed to nitric oxide releasing particles comprising a mesoporous silica network. Also disclosed are compositions comprising one or more nitric-oxide releasing particles and a polymer. In one aspect, the particles are admixed with the polymer. The compositions exhibit high payloads of nitric oxide release without particle leaching or the need for extremely cold storage conditions.

Extended nitric oxide-releasing polymers via functionalized mesoporous silica nanoparticles

Several embodiments of NO releasing structures are disclosed. In some embodiments, the structures are covalently modified to store and release nitric oxide. Some embodiments pertain to methods of making and use of these structures. The covalently modified polymer structures may be tailored to release nitric oxide in a controlled manner and are useful for treatment of various medical conditions.

Nitric oxide-releasing antibacterial polymers and scaffolds fabricated therefrom and methods pertaining thereto

Provided herein are hyperbranched polyaminoglycosides, where in some embodiments, the hyperbranched polyaminoglycosides are covalently modified to store and release nitric oxide. Some embodiments pertain to methods of making and use of hyperbranched polyaminoglycosides. In some embodiments, the covalently modified hyperbranched polyaminoglycosides may be tailored to release nitric oxide in a controlled manner and are useful for eradication of both gram positive and gram negative bacteria as well as other microbes.

Nitric oxide-releasing polyaminoglycosides as biodegradable antibacterial scaffolds and methods pertaining thereto

Large molecular weight alginates which are covalently modified to store and release nitric oxide, as well as methods of making and use thereof, are disclosed herein. The covalently modified alginates may be tailored to release nitric oxide in a controlled manner and are useful for eradication of both planktonic and biofilm-based bacteria.

Nitric oxide-releasing alginates as biodegradable antibacterial scaffolds and methods pertaining thereto

The presently disclosed subject matter relates to nitric oxide-releasing particles for delivering nitric oxide, and their use in biomedical and pharmaceutical applications.

Nitric oxide-releasing particles for nitric oxide therapeutics and biomedical applications

Disclosed herein are cyclodextrin molecules covalently modified to store and release nitric oxide, as well as methods of making and uses thereof. The covalently modified cyclodextrin molecules may be tailored, in several embodiments, to release nitric oxide in a controlled manner and are useful for reduction and/or eradication of bacteria and for the treatment of disease.

Nitric oxide-releasing cyclodextrins as biodegradable antibacterial scaffolds and methods pertaining thereto

Nitric oxide-releasing mesoporous silica nanoparticles (MSNs) were prepared using an aminosilane-template surfactant ion exchange reaction. Initially, bare silica particles were synthesized under basic conditions in the presence of cetyltrimethylammonium bromide (CTAB). These particles were functionalized with nitric oxide (NO) donor precursors via the addition of aminosilane directly to the particle sol, and a commensurate ion exchange reaction between the cationic aminosilanes and CTAB. N-diazeniumdiolate NO donors were formed at the secondary amines to yield NO-releasing silica MSNs. Tuning of the ion exchange-based MSN modification approach allowed for the preparation of monodisperse particles ranging from 30 to 1100 nm. Regardless of size, the MSNs stored appreciable levels of NO (0.4-1.5 &#x3bc;mol/mg) with tunable NO-release durations (1-33 h) dependent on the aminosilane modification. The range of MSN sizes and NO release demonstrate the versatility of this strategy.

Functionalized mesoporous silica via an aminosilane surfactant ion exchange reaction: controlled scaffold design and nitric oxide release

Provided herein are compounds, compositions, and methods for modifying mucus, including modifying mucus using nitric oxide-releasing biopolymers (e.g., NO-releasing chitosan oligosaccharides). In some embodiments, a compound, composition, and/or method of the present invention modifies one or more properties of mucus to increase mucus clearance in a subject and/or prevents the growth or kills one or more pathogens present in mucus of a subject.

Compounds, compositions and methods for inhibiting a pathogen and/or modifying mucus

The invention generally relates to compositions comprising degradable polymers and methods of making degradable polymers. Specifically, the disclosed degradable polymers comprise a biodegradable polymer backbone, a nitric oxide linker moiety, and a nitric oxide molecule. This abstract is intended as a scanning tool for purposes of searching in the particular art and is not intended to be limiting of the present invention.

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Chapel Hill, NC, United States of America

Mark H Schoenfisch