State of the art, challenges and perspectives in the design of nitric oxide-releasing polymeric nanomaterials for biomedical applications

Seabra, Amedea B.; Justo, Giselle Z.; Haddad, Paula S.

doi:10.1016/j.biotechadv.2015.01.005

Cited by 129 publications

(104 citation statements)

References 101 publications

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“…Macromolecular scaffolds capable of effectively storing and releasing NO have been developed to enable local delivery (27,28). The most promising NO release vehicles to date include NO donor-modified N-diazeniumdiolate silica nanoparticles (29)(30)(31), dendrimers (32)(33)(34)(35)(36), and chitosan (15).…”

mentioning

confidence: 99%

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

Reighard

2015

Antimicrob Agents Chemother

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Chitosan oligosaccharides were modified with N-diazeniumdiolates to yield biocompatible nitric oxide (NO) donor scaffolds. The minimum bactericidal concentrations and MICs of the NO donors against Pseudomonas aeruginosa were compared under aerobic and anaerobic conditions. Differential antibacterial activities were primarily the result of NO scavenging by oxygen under aerobic environments and not changes in bacterial physiology. Bacterial killing was also tested against nonmucoid and mucoid biofilms and compared to that of tobramycin. Smaller NO payloads were required to eradicate P. aeruginosa biofilms under anaerobic versus aerobic conditions. Under oxygen-free environments, the NO treatment was 10-fold more effective at killing biofilms than tobramycin. These results demonstrate the potential utility of NO-releasing chitosan oligosaccharides under both aerobic and anaerobic environments. Pseudomonas aeruginosa is an opportunistic human pathogen that frequently colonizes people with compromised immune systems, such as those with cystic fibrosis (CF) or severe burn wounds (1). The success of P. aeruginosa as a pathogen is related to its multitude of virulence factors, which increase adherence to the host cells, induce inflammation, and disrupt the host immune response (1). Furthermore, P. aeruginosa is intrinsically resistant to many antibiotics due to low membrane permeability and increased expression of ␤-lactamases and efflux pumps (2-4). In addition to this native resistance, P. aeruginosa readily adapts to antibiotic challenge by acquiring resistance genes (3, 5) and forming protective, cooperative communities known as biofilms (6, 7).While all antibiotic resistance mechanisms are not fully understood, at least three main factors reduce antibiotic efficacy against bacterial biofilms compared to planktonic cells. First, P. aeruginosa in biofilms secretes a protective layer of exopolysaccharides that prevent the diffusion of antibiotics (7). In the context of cystic fibrosis, biofilm-bound P. aeruginosa exists predominantly as the mucoid phenotype, characterized by a secreted alginate matrix that provides a physical barrier against the host immune response and antibiotics (8). This exopolysaccharide matrix also prevents the diffusion of oxygen into biofilms, causing P. aeruginosa to switch from aerobic to anaerobic respiration (9). The reduced metabolic activity of P. aeruginosa undergoing anaerobic respiration protects the bacterium against traditional antibiotics that are most effective against rapidly dividing cells, including aminoglycosides and ␤-lactams (10, 11). Finally, biofilms produce persister cells (i.e., dormant bacteria that are highly resistant to chemical disinfectants and exhibit multidrug tolerance) much more frequently than planktonic bacterial cultures (3, 7).The failure of conventional antibiotics to treat P. aeruginosa biofilms and infections necessitates the development of new antibacterial agents. Nitric oxide (NO), an endogenously produced free radical that can disperse (12, 13) and ...

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confidence: 99%

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

Reighard

2015

Antimicrob Agents Chemother

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“…[31] Organic nitrate and nitrites Organic nitrate and nitrite esters are the first generation of nitrovasodilators applied in clinical for NO-targeting therapies. The general formulae for organic nitrates and nitrites are RONO 2 and RONO, respectively, where R is an aryl or alkyl group. Organic nitrates and nitrites are primarily used for the treatment of angina symptoms because they can produce NO from the metabolism within the endothelium.…”

Section: No Donors For Biomedical and Therapeutic Applicationsmentioning

confidence: 99%

“…Indeed, accumulating evidence supports the pivotal role for NO as an efficient inhibitor of restenosis, a simple key molecule involved in accelerated wound repair and an anticancer and antibacterial agent. [2] Various disease and lifestyle factors for cardiovascular diseases (CVDs) are associated with NO-signaling pathways ( Fig. 1), [3] and benefits from the mostly acceptable lifestyles and cardiovascular therapies are due to the release of NO.…”

Section: Introductionmentioning

confidence: 99%

Modulated nitric oxide delivery in three-dimensional biomaterials for vascular functionality

et al. 2017

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Nitric oxide (NO) acts a pivotal role in regulating various physiological processes of vasodilation, platelet aggregation, and vascular smooth muscle cell mitogenesis and proliferation. This makes NO a promising candidate for the treatment of cardiovascular problems like hypertension and vascular stenosis. However, the high reactivity of NO poses an issue for effective NO delivery. To overcome this limitation, recent developments on three-dimensional (3D) materials have been explored with either physical or chemical incorporation of NO releasing donors, to provide spatiotemporal control over NO-signaling pathways in blood vessels. Here, we offer an overview on the current efforts, and propose future perspectives for precise regulation on NO delivery in advanced 3D materials toward proper vascular functionality.

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“…13 A diverse range of carriers have been reported including silica particles, metal and protein nanoparticles, dendrimers, star polymers and micelles. 18 The physical encapsulation of NO donors often leads to premature dose dumping. copolymer) are unique NO delivery vehicles.…”

Section: Introductionmentioning

confidence: 99%

Nitric oxide-releasing graft polymer micelles with distinct pendant amphiphiles

et al. 2015

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Polymeric micelle is a versatile nanoscale platform for sustained release of short-lived nitric oxide (NO). The aim of this work was to better understand the correlation between polymer architecture and NO release kinetics. Stable nitrate was selected as the NO donor and co-conjugated to a multivalent polymer backbone together with amphiphilic methoxy poly(ethylene glycol) and poly(lactic acid) (mPEG-PLA), or D-α-tocopheryl polyethylene glycol 1000 succinate (TPGS). Both graft polymers could self-assemble into micellar nanocarriers with a size less than 100 nm. The weight-based NO loading was 4.92% (w/w) and 6.05% (w/w) for mPEG-PLA-and TPGS-modified micelles, respectively. The former is less stable than the later with a corresponding critical micelle concentration of 23.9 ± 2.0 nM and 9.8 ± 0.5 nM. Using the standard Griess assay, it was shown that both micelles could achieve sustained NO release in vitro. However, the TPGS-modified nanocarrier exhibited a delayed onset, but faster steady-state release of NO in comparison to its counterpart. This was primarily due to folded PEG conformation and its high packing surface density. These results illustrate the potential utility of polymer architecture engineering to precisely tune the NO release behavior for ultimately optimum therapeutic outcome.

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State of the art, challenges and perspectives in the design of nitric oxide-releasing polymeric nanomaterials for biomedical applications

Cited by 129 publications

References 101 publications

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

Antibacterial Action of Nitric Oxide-Releasing Chitosan Oligosaccharides against Pseudomonas aeruginosa under Aerobic and Anaerobic Conditions

Modulated nitric oxide delivery in three-dimensional biomaterials for vascular functionality

Nitric oxide-releasing graft polymer micelles with distinct pendant amphiphiles

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