Combined Antibacterial and Anti-Inflammatory Activity of a Cationic Disubstituted Dexamethasone-Spermine Conjugate

Bucki, Robert; Leszczyńska, Katarzyna; Byfield, Fitzroy J.; Fein, David E.; Won, Esther; Cruz, Katrina; Namiot, Andrzej; Kułakowska, Alina; Namiot, Z; Savage, Paul B.; Diamond, Scott L.; Janmey, Paul A.

doi:10.1128/aac.01682-09

Cited by 21 publications

(19 citation statements)

References 54 publications

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“…To compare the bactericidal activities of CSA-13 (0.7 μg/ml) and MNP-CSA-13 (5 μg/ml) and MNPs themselves (4.3 μg/ml) against P. aeruginosa PAO14, killing assay/CFU counting method was performed [ 58 ]. The concentrations of tested agents were calculated to added equal amount of free CSA-13 and CSA-13 molecules attached to the MNP surface.…”

Section: Methodsmentioning

confidence: 99%

Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles

et al. 2015

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BackgroundCeragenins, synthetic mimics of endogenous antibacterial peptides, are promising candidate antimicrobial agents. However, in some settings their strong bactericidal activity is associated with toxicity towards host cells. To modulate ceragenin CSA-13 antibacterial activity and biocompatibility, CSA-13-coated magnetic nanoparticles (MNP-CSA-13) were synthesized. Transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) were used to characterize MNP-CSA-13 physicochemical properties. Bactericidal action and ability of these new compounds to prevent Pseudomonas. aeruginosa biofilm formation were assessed using a bacteria killing assay and crystal violet staining, respectively. Release of hemoglobin from human red blood cells was measured to evaluate MNP-CSA-13 hemolytic activity. In addition, we used surface activity measurements to monitor CSA-13 release from the MNP shell. Zeta potentials of P. aeruginosa cells and MNP-CSA-13 were determined to assess the interactions between the bacteria and nanoparticles. Morphology of P. aeruginosa subjected to MNP-CSA-13 treatment was evaluated using atomic force microscopy (AFM) to determine structural changes indicative of bactericidal activity.ResultsOur studies revealed that the MNP-CSA-13 nanosystem is stable and may be used as a pH control system to release CSA-13. MNP-CSA-13 exhibits strong antibacterial activity, and the ability to prevent bacteria biofilm formation in different body fluids. Additionally, a significant decrease in CSA-13 hemolytic activity was observed when the molecule was immobilized on the nanoparticle surface.ConclusionOur results demonstrate that CSA-13 retains bactericidal activity when immobilized on a MNP while biocompatibility increases when CSA-13 is covalently attached to the nanoparticle.

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Section: Methodsmentioning

confidence: 99%

Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles

et al. 2015

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“…49,50 Also, some works have related that dexamethasone and some dexamethasone-based derivatives present antimicrobial action. 51,52 However, for treating skin diseases, dexamethasone is usually administrated with gentamycin (an antibiotic with strong antimicrobial activity that provides an acute kidney injury). 18,53 Dexamethasone and antibiotics cause several side effects on health.…”

Section: Adhesion and Proliferation Testmentioning

confidence: 99%

Chitosan Imparts Better Biological Properties for Poly(ε-caprolactone) Electrospun Membranes than Dexamethasone

Machado

Roberto

Bonafé

et al. 2019

J. Braz. Chem. Soc.

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Poly(ε-caprolactone), an aliphatic polyester with biodegradability and cytocompatibility, has been used to create scaffolds for tissue engineering purposes. However, the hydrophobicity and low water absorptivity of poly(ε-caprolactone) reduce cell anchorage on their membranes. Here, poly(ε-caprolactone)-based scaffolds were prepared by electrospinning of poly(ε-caprolactone)chitosan blend, and poly(ε-caprolactone)-dexamethasone solution. Chitosan and dexamethasone play an essential role to increase the scaffolding performance of poly(ε-caprolactone)-based electrospun membranes. A poly(ε-caprolactone) membrane without chitosan and dexamethasone did not provide satisfactory results to promote cell culture of adipose mesenchymal stem cells (AMSCs). Compared to the poly(ε-caprolactone)-dexamethasone surface, poly(ε-caprolactone)chitosan membrane imparts better cytoskeletal reorganization, and cell spreading, increasing the strength of cell attachment. Also, poly(ε-caprolactone)-chitosan composite provides strong antimicrobial activity against Pseudomonas aeruginosa (ca. 90% inhibition). Therefore, the poly(ε-caprolactone)-chitosan composite is a better alternative to treat skin diseases and promote skin regeneration than conventional approaches based on dexamethasone.

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“…Coupling an antibody specific to the outer surface of P. gingivalis strain 381 to SMAP28 selectively kills P. gingivalis in an artificially generated microbial community containing P. gingivalis, Aggregatibacter actinomycetemcomitans and Peptostreptococcus micros [108]. Furthermore, a disubstituted dexamethasone–spermine conjugate kills S. aureus and P. aeruginosa , enhances S. aureus susceptibility to antibiotics, and inhibits interleukin (IL)-6 and IL-8 release from LPS- or LTA-treated neutrophils [112]. …”

Section: Modified Antimicrobial Peptidesmentioning

confidence: 99%

Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?

Brogden

2011

International Journal of Antimicrobial Agents

193

210

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The concept of antimicrobial peptides (AMPs) as potent pharmaceuticals is firmly established in the literature, and most research articles on this topic conclude by stating that AMPs represent promising therapeutic agents against bacterial and fungal agents. Indeed, early research in this field showed that AMPs were diverse in nature, had high activities with low minimal inhibitory concentrations, had broad spectrums of activity against bacterial, fungal and viral pathogens, and could easily be manipulated to alter their specificities, reduce their cytotoxicities and increase their antimicrobial activities. Unfortunately, commercial development of these peptides, for even the simplest of applications, has been very limited. With some peptides there are obstacles with their manufacture, in vivo efficacy and in vivo retention. More recently, the focus has shifted. Contemporary research now uses a more sophisticated approach to develop AMPs that surmount many of these prior obstacles. AMP mimetics, hybrid AMPs, AMP congeners, cyclotides and stabilised AMPs, AMP conjugates and immobilised AMPs have all emerged with selective or ‘targeted’ antimicrobial activities, improved retention, or unique abilities that allow them to bind to medical or industrial surfaces. These groups of new peptides have creative medical and industrial application potentials to treat antibiotic-resistant bacterial infections and septic shock, to preserve food or to sanitise surfaces both in vitro and in vivo.

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Combined Antibacterial and Anti-Inflammatory Activity of a Cationic Disubstituted Dexamethasone-Spermine Conjugate

Cited by 21 publications

References 54 publications

Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles

Bactericidal activity and biocompatibility of ceragenin-coated magnetic nanoparticles

Chitosan Imparts Better Biological Properties for Poly(ε-caprolactone) Electrospun Membranes than Dexamethasone

Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?

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