Abstract:The antibiotic ciprofloxacin (CIP) was covalently attached to the chain end of poly(2-methyloxazoline) (PMOx), poly(2-ethyloxazoline) (PEtOx), and polyethylene glycol (PEG), and the antimicrobial activity of these conjugates was tested for Staphylococcus aureus, Streptococcus mutans, Escherichia coli, Pseudomonas aeruginosa, and Kleisella pneumoniae. Chemical structures of the conjugates were proven by (1)H NMR and electron spray ionization mass spectrometry. The direct coupling of PMOx and CIP resulted in low… Show more
“…Several independent studies show that poly(2‐ethyl‐2‐oxazoline) (PETOx) and poly(2‐methyl‐2‐oxazoline) (PMeOx) exhibit very low cytotoxicity and have no other side effects in immune systems . Moreover, even PETOx containing a certain amount of functional groups did not demonstrate any in vitro cytotoxic effects . Recent studies on a hemotoxicity of PMeOx and PETOx conjugates with enzymes and drugs confirmed even higher values of their hemolytic concentration with 50% red blood cells lysed (HC 50 ) compared to poly(ethylene glycol) (PEG) conjugates .…”
Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes. The cytotoxicities of 2-oxazoline monomers, PIPOx, and fluorescently labeled PIPOx are evaluated in vitro using an 3-(4,5-Dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and ex vivo using a cell proliferation assay with adenosine triphosphate bioluminescence. The cell uptake of labeled PIPOx is used to determine the colocalization of PIPOx with cell organelles that are part of the endocytic pathway. For the first time, it is shown that poly(2-isopropenyl-2-oxazoline) is a biocompatible material and is suitable for biomedical applications; further, its immunomodulative properties are evaluated.
“…Several independent studies show that poly(2‐ethyl‐2‐oxazoline) (PETOx) and poly(2‐methyl‐2‐oxazoline) (PMeOx) exhibit very low cytotoxicity and have no other side effects in immune systems . Moreover, even PETOx containing a certain amount of functional groups did not demonstrate any in vitro cytotoxic effects . Recent studies on a hemotoxicity of PMeOx and PETOx conjugates with enzymes and drugs confirmed even higher values of their hemolytic concentration with 50% red blood cells lysed (HC 50 ) compared to poly(ethylene glycol) (PEG) conjugates .…”
Poly(2-alkenyl-2-oxazoline)s are promising functional polymers for a variety of biomedical applications, such as drug delivery systems, peptide conjugates, or gene delivery. In this study, poly(2-isopropenyl-2-oxazoline) (PIPOx) is prepared through free-radical polymerization initiated with azobisisobutyronitrile. Reactive 2-oxazoline units in the side chain support an addition reaction with different compounds containing a carboxylic group, which facilitates the preparation of polymers labeled with two different fluorescent dyes. The cytotoxicities of 2-oxazoline monomers, PIPOx, and fluorescently labeled PIPOx are evaluated in vitro using an 3-(4,5-Dimethyldiazol-2-yl)-2,5-diphenyl tetrazolium bromide assay and ex vivo using a cell proliferation assay with adenosine triphosphate bioluminescence. The cell uptake of labeled PIPOx is used to determine the colocalization of PIPOx with cell organelles that are part of the endocytic pathway. For the first time, it is shown that poly(2-isopropenyl-2-oxazoline) is a biocompatible material and is suitable for biomedical applications; further, its immunomodulative properties are evaluated.
“…For example, Du et al (29) conjugated PEG (5,000 Da) to tobramycin and reported increased efficacy against in vivo Pseudomonas aeruginosa biofilm. Another study showed that ciprofloxacin could be conjugated to PEG (2,000 Da), and this enhanced antibiotic efficacy against both Gram-negative and -positive bacteria (30). Our experiments did not involve conjugation between the osmotic agents and antibiotics, although this is probably requisite for successful applications in vivo.…”
Biofilm-associated infections are a clinical challenge, in part because a hydrated matrix protects the bacterial community from antibiotics. Herein, we evaluated how different osmotic compounds (maltodextrin, sucrose, and polyethylene glycol [PEG]) enhance antibiotic efficacy against biofilm communities. Established (24-h) test tube biofilms (strain ATCC 17978) were treated with osmotic compounds in the presence or absence of 10× the MIC of different antibiotics (50 μg/ml tobramycin, 20 μg/ml ciprofloxacin, 300 μg/ml chloramphenicol, 30 μg/ml nalidixic acid, or 100 μg/ml erythromycin). Combining antibiotics with hypertonic concentrations of the osmotic compounds for 24 h reduced the number of biofilm bacteria by 5 to 7 log ( < 0.05). Increasing concentrations of osmotic compounds improved the effect, but there was a trade-off with increasing solution viscosity, whereby low-molecular-mass compounds (sucrose, 400-Da PEG) worked better than higher-mass compounds (maltodextrin, 3,350-Da PEG). Ten other strains were similarly treated with 400-Da PEG and tobramycin, resulting in a mean 2.7-log reduction in recoverable bacteria compared with tobramycin treatment alone. Multivariate regression models with data from different osmotic compounds and nine antibiotics demonstrated that the benefit from combining hypertonic treatments with antibiotics is a function of antibiotic mass and lipophilicity ( > 0.82; < 0.002), and the relationship was generalizable for biofilms formed by and K-12. Augmenting topical antibiotic therapies with a low-mass hypertonic treatment may enhance the efficacy of antibiotics against wound biofilms, particularly when using low-mass hydrophilic antibiotics. Biofilms form a barrier that protects bacteria from environmental insults, including exposure to antibiotics. We demonstrated that multiple osmotic compounds can enhance antibiotic efficacy against biofilm communities, but viscosity is a limiting factor, and the most effective compounds have lower molecular mass. The synergism between osmotic compounds and antibiotics is also dependent on the hydrophobicity and mass of the antibiotics. The statistical models presented herein provide a basis for predicting the optimal combination of osmotic compounds and antibiotics against surface biofilms communities.
“…The hemocompatibility of the prepared polymers was explored and HC 50 (hemolytic concentration at with 50% blood cells is lysed) was determined with use of porcine blood cells. All values were above 5000 µg/cm 3 indicating low hemotoxicity of the conjugates obtained [42].
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Section: Polymersmentioning
confidence: 99%
“…Poly(2-oxazoline)s (POx) are also non-toxic polymers with adjustable hydrophilicity and easily modified end-groups [ 41 ]. The antibiotic ciprofloxacin was covalently attached to the chain of poly(2-methyloxazoline) (PMOx), poly(2-ethyloxazoline) (PEtOx), and PEG (Scheme 4 ) [ 42 ]. Anti-microbial activity of the novel conjugates was tested against S. aureus , Streptococcus mutans , E. coli , P. aeruginosa, and K. pneumoniae .…”
This review is aimed to provide extensive survey of quinolones and fluoroquinolones for a variety of applications ranging from metal complexes and nanoparticle development to hybrid conjugates with therapeutic uses. The review covers the literature from the past 10 years with emphasis placed on new applications and mechanisms of pharmacological action of quinolone derivatives. The following are considered: metal complexes, nanoparticles and nanodrugs, polymers, proteins and peptides, NO donors and analogs, anionic compounds, siderophores, phosphonates, and prodrugs with enhanced lipophilicity, phototherapeutics, fluorescent compounds, triazoles, hybrid drugs, bis-quinolones, and other modifications. This review provides a comprehensive resource, summarizing a broad range of important quinolone applications with great utility as a resource concerning both chemical modifications and also novel hybrid bifunctional therapeutic agents.Graphical abstract
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