Gatifloxacin Research Articles

Spectroscopic study of the interaction between adenosine disodium triphosphate and gatifloxacin-Al3+ complex and its analytical application.

A new and sensitive spectrofluorimetric method has been proposed to determine trace amount of adenosine disodium triphosphate (ATP). The method is based on the fluorimetric interaction between gatifloxacin (GFLX)-aluminium (III) (Al(3+) ) complex and ATP and studied using UV-visible and fluorescence spectroscopy. Weak luminescence spectra of Al(3+) were enhanced after complexation with GFLX at 423 nm upon excitation at 272 nm due to energy transfer from the ligand to the Al(3+) ion. It was observed that the FL emission spectrum of GFLX-Al(3+) was enhanced significantly by the addition of ATP. Under the optimal conditions, the enhancement of FL intensity at 423 nm was responded linearly with the concentration of ATP in the range 1.3 × 10(-10) - 1.0 × 10(-8) mol L(-1) with correlation coefficient (r) of 0.9981. The limit of detection (LOD) was found to be 1.1 × 10(-11) mol L(-1) for ATP with the standard deviation (RSD) of 1.21% for five repeated measurement of 2.3 × 10(-8) mol L(-1) ATP. The presented method is simple, sensitive, free from coexisting interferents and can be applied successfully to determine ATP in the real samples.

Nontuberculous mycobacterial ocular infections--comparing the clinical and microbiological characteristics between Mycobacterium abscessus and Mycobacterium massiliense.

PurposeTo analyze the clinical characteristics of nontuberculous mycobacterial (NTM) ocular infections and the species-specific in vitro antimicrobial susceptibility.Material and MethodsIn 2000 to 2011 at the National Taiwan University Hospital, multilocus sequencing of rpoB, hsp65 and secA was used to identify NTM isolates from ocular infections. The clinical presentation and treatment outcomes were retrospectively compared between species. Broth microdilution method was used to determine the minimum inhibitory concentrations of amikacin (AMK), clarithromycin (CLA), ciprofloxacin (CPF), levofloxacin (LVF), moxifloxacin (MXF) and gatifloxacin (GAF) against all strains. The activities of antimicrobial combinations were assessed by the checkerboard titration method.ResultsA total of 24 NTM strains (13 Mycobacterium abscessus and 11 Mycobacterium massiliense) were isolated from 13 keratitis, 10 buckle infections, and 1 canaliculitis cases. Clinically, manifestations and outcomes caused by these two species were similar and surgical intervention was necessary for medically unresponsive NTM infection. Microbiologically, 100% of M. abscessus and 90.9% of M. massiliense ocular isolates were susceptible to amikacin but all were resistant to fluoroquinolones. Inducible clarithromycin resistance existed in 69.3% of M. abscessus but not in M. massiliense isolates. None of the AMK-CLA, AMK-MXF, AMK-GAF, CLA-MXF and CLA-GAF combinations showed synergistic or antagonistic effect against both species in vitro.Conclusions M. abscessus and M. massiliense are the most commonly identified species for NTM ocular infections in Taiwan. Both species were resistant to fluoroquinolones, susceptible to amikacin, and differ in clarithromycin resistance. Combined antimicrobial treatments showed no interaction in vitro but could be considered in combination with surgical interventions for eradication of this devastating ocular infection.

Alterations in Biochemical Indices and Antioxidant Status in Rats Following Treatment with Gatifloxacin

Aim: Gatifloxacin (GTX) - an 8 - methoxy fluoroq uinolone antibacterial agent has been considered very effective in the treatment of respiratory and urinary tract infections. This study investigates the toxic potentials of GTX in Wistar rats. Methodology: Twenty male rats (180 - 220 g) were randomised int o four groups: I - Control, II - 4 mg/kg body weight (b.w.) GTX, III - 8 mg/kg b.w GTX, and IV - 16 mg/kg b.w GTX. Results: After seven days of GTX administration, the levels of plasma creatinine, urea and bilirubin were increased significantly ( P< 0.05 ) in GTX - tr eated rats compared to control. ALP, ALT, AST and GGT activities were also elevated significantly in the plasma of the treated animals relative to control. Similarly, hepatic malondialdehyde level increased significantly in the GTX treated groups relative to control. Hepatic levels of ascorbic acid, reduced glutathione as well as activities of hepatic GST, catalase, and SOD were reduced significantly in a dose dependent manner in the GTX - treated animals compared to control. Besides, histopathological studie s revealed very mild, moderate and severe hepatic portal congestion and cellular infiltration by mononuclear cells by the three doses of GTX. Conclusion: Overall, three different doses of Gatifloxacin (half - therapeutic, therapeutic and double - therapeutic) induced renal and hepatic damages, as well as oxidative stress in rats. Original Research Article

Effects of gatifloxaine content in gatifloxacine-loaded PLGA and β-tricalcium phosphate composites on efficacy in treating osteomyelitis.

Composites of gatifloxacin (GFLX)-loaded poly (lactic-co-glycolic) acid (PLGA) and β-tricalcium phosphate (βTCP) containing 0, 1, and 10 wt % GFLX (0, 1, and 10 wt % GFLX composites), and GFLX-loaded PLGA containing 1, 5, and 10 wt % GFLX (1, 5, and 10wt % GFLX-PLGA) as controls were fabricated and characterized in vitro and in vivo. On in vitro evaluation, the 10 wt % GFLX composite released GFLX over at least 28 days in Hanks' balanced solution and exhibited clinically sufficient bactericidal activities against Streptococcus milleri and Bacteroides fragilis from 1 h to 10 days. The 0, 1, and 10 wt % GFLX composites and 10 wt % GFLX-PLGA were implanted in bone defects created by debridement of osteomyelitis lesions induced by S. milleri and B. fragilis in the mandible of rabbits (n = 5). Four weeks after implantation of the 10 wt % GFLX composite, inflammation in the debrided area disappeared in all the rabbits, while inflammation remained in all the rabbits after implantation of the 0 wt % GFLX composite and 10 wt % GFLX-PLGA, and in three rabbits after implantation of the 1 wt % GFLX composite. Bone formation appears to be less intense for the 10 wt % GFLX composite than for the 1 wt % GFLX composite probably owing to the rapid degradation of the 10 wt % GFLX composite. These findings show that the GFLX composite is effective for the local treatment of osteomyelitis.

Resistencia a drogas de segunda línea en cepas peruanas de Mycobacterium tuberculosis multidrogorresistentes

To determine the drug resistance profiles for quinolones: ciprofloxacin (CFX), ofloxacin (OFX), moxifloxacin (MFX), and gatifloxacin (GFX); and for injectables: kanamycin (KAN), amikacin (AMK), and capreomycin (CAP) in multidrug resistant (MDR) strains. We also investigated the correlation between mutations in rrs, tlyA and gyrA/B genes, and the in vitro resistance to the second-line anti-tuberculosis drugs. In this pilot study we selected MDR clinical isolates collected from June-December 2004 in the Tropical Medicine Institute "Alexander von Humboldt" (Lima, Perú). The Minimum Inhibitory Concentration (MIC) of CFX, OFX, MFX, GFX, KAN, AMK and CAP for 14 clinical isolates were determined and the sequences of rrs, tlyA and gyrA/B genes were analyzed by conventional PCR followed by sequencing. We obtained valid results for 11 samples. Four isolates were resistant to injectable drugs, and in all the cases the MICs were; >120 µg/mL for KAN and >160 µg/mL for AMK and CAP. Only 2 isolates were resistant to OFX with MIC = 4 µg/mL. Sequencing results suggested that the mutation A1401T in rrs gene could be the molecular cause of the resistance to injectable drugs. In this study we did not find any mutation in tlyA and gyrA/B associated to resistance. Our study suggests a possible association between the mutation A1401T in rrs and resistance to injectable drugs. However further studies should be done to confirm this hypothesis in Perú.

Successful '9-month Bangladesh regimen' for multidrug-resistant tuberculosis among over 500 consecutive patients.

Tuberculosis (TB) program, Damien Foundation Projects, Bangladesh. To summarize the outcome and its determinants of the first treatment for multidrug-resistant TB using a standardized regimen consisting of a minimum 9 months. This was a prospective, observational study of a gatifloxacin (GFX) based directly observed regimen, mainly with initial hospitalization. The 4-month intensive phase was extended until sputum smear conversion. Patients were monitored using culture for up to 2 years after treatment completion. Of the 515 patients who met the study inclusion criteria and were successively enrolled from 2005 to 2011, 84.4% had a bacteriologically favorable outcome. Due to extensive disease with delayed sputum conversion, only half of the patients completed treatment within 9 months; however, 95% were able to complete treatment within 12 months. Eleven patients failed or relapsed, and 93.1% of the 435 patients who were successfully treated completed at least 12 months post-treatment follow-up. The strongest risk factor for a bacteriologically unfavorable outcome was high-level fluoroquinolone (FQ) resistance, particularly when compounded by initial pyrazinamide (PZA) resistance. Low-level FQ resistance had no unfavorable effect on treatment outcome. Amplification of drug resistance occurred only once, in a patient strain that was initially only susceptible to kanamycin and clofazimine. The excellent outcome of the Bangladesh regimen was largely maintained. Bacteriological treatment failures and relapses were rare, except among patients with high-level GFX resistance, notably in the presence of PZA resistance.

Development of a flow-injection analysis system with fluorescence detection for gatifloxacin determination in organized medium.

This work reports the development and optimization of a flow injection analysis system with fluorescence detection (FIA-FLUO) for gatifloxacin (GFX) determination in organized medium. The analytical system was based on the enhanced fluorescence of gatifloxacin in micellar medium containing sodium dodecyl sulfate (SDS) at pH 6.0. The influence of physical (carrier flow rate, sample volume and volume of reaction coil) and chemical (pH, concentration of buffer and concentration of SDS) parameters that could affect the performance of the FIA system was evaluated in order to reach optimum conditions in terms of sensitivity and analytical throughput. Under optimized conditions, the FIA-FLUO system allowed the injection of 40 samples per hour with a limit of quantification of 72 µg/L and a RSD of 3.5% at 0.20 mg/L. Real samples of commercial pharmaceutical formulations containing GFX were analyzed, and no statistical difference was observed between the results obtained using the developed system and those obtained using the reference method based on high-performance liquid chromatography with UV detection.

Experimental study of iontophoresis-mediated corneal collagen crosslinking for rabbit Staphylococcus aureus keratitis

Background It is determined that riboflavin/ultraviolet A (UVA)-induced corneal collagen crosslinking is able to increase resistance of cornea against enzymatic digestion and has antimicrobial efficacy for various kinds of bacteria in vitro.However,its in vivo study is less now.Objective This study aimed to evaluate the efficacy of iontophoresis-mediated corneal collagen crosslinking combined with or without drugs for Staphylococcus aureus keratitis.Methods Bacterial keratitis models were induced by the interstromaly injection of Staphylococcus aureus suspension with concentration 2× 109/ml in the right eyes of 40 rabbits,and then the rabbits were randomly classified into the model group,gatifloxacin eye drops group,riboflavin/UVA corneal crosslinking group and drugs+ crosslinking group.The smearing of corneal surface was performed for the identification of bacteria 24 hours after injection.Iontophoresis-mediated riboflavin/UVA crosslinking was applied on the eyes of the riboflavin/UVA corneal crosslinking group and drugs+crosslinking group,and gatifloxacin eye drops was topically used 7 times per day on the eyes of the gatifloxacin eye drops group and drugs+crosslinking group.The corneal inflammation was examined and graded under the slit lamp biomicroscope before and after treatment.Ocular anterior segment optical coherence tomography(AS-OCT),corneal histopathology and ultrastructure were examined 14 days after treatment.The living environment of the experimental animals was maintained at 21 ℃ with a 12-hour light and dark cycle.Animals used in this study were treated in accordance with the Weifang Medical College Animal Experimentation Ethic Committee (AEEC) guidelines.The study protocol was approved by the AEEC.Results Corneal inflammation and ulcer were observed,but no significant difference was found in the inflammatory grade among the 4 groups 24 hours after injection (x2=0.293,P＞0.05).In the 14th day after injection,the corneal ulcer area was smaller and corneal edema was milder in the drugs+crosslinking group compared with the model group,gatifloxacin eye drops group and riboflavin/ UVA corneal crosslinking group,showing a significant difference in the inflammatory grade among them (x2 =38.710,P＜0.001).The cornea thickness values of ulcer zone were (428.1 ± 146.2) μm on the 14th postinjected day in the drugs+crosslinking group,which was evidently higher than those in the model group,gatifloxacin eye drops group and riboflavin/UVA corneal crosslinking group,with a significant difference among the 4 groups (F =8.310,P＜0.001).A lower degree of destruction of cornea collagen and less inflammatory cells were seen in the cornea tissue of the drugs+ crosslinking group by haematoxylin and eosin staining in comparison with other 3 groups,and normal keratocytes were much more in the drugs + crosslinking group than those in other treated groups.Conclusions Iontophoresismediated corneal collagen crosslinking can alleviate Staphylococcus aureus keratitis.The combination of crosslinking with drugs has a better effectiveness than the administration of gatifloxacin eye drops only or riboflavin/UVA corneal crosslinking only. Key words: Iontophoresis; Collagen crosslinking; Ultraviolet ray; Cross-linking reagent; Riboflavin; Staphylococcus aureus ; Keratitis

Polyoxometalate cobalt–gatifloxacin complex with DNA binding and antibacterial activity

An unusual inorganic–organic antibacterial complex based on polyoxometalates (POMs) and the cobalt–gatifloxacin (GT), [CoII(C19FH22N3O4)3][C19FH23N3O4][HSiW12O40]·23H2O (1), has been synthesized. Single-crystal structural analysis shows that 1 represents for the first time an unusual tripodal coordination style with three GT molecules coordinating to cobalt(II) by six carboxylate and hydroxyl oxygens. The biological activity of 1 has been evaluated by investigating its binding ability to calf thymus DNA (CT-DNA). UV spectrum study of 1 has shown that it can bind to CT-DNA by intercalation. The DNA-binding constant Kb was 9.6 × 104 M L−1, higher than that of pure GT, 3.8 × 104 M L−1. Furthermore, the antibacterial activities of 1 were tested against Staphylococcus aureus and Escherichia coli, respectively, and have shown slightly lower antibacterial activity than that of free GT at the same mass concentration. If the GT component in the complexes was controlled at the same molar concentration, 1 generates the biggest antibacterial area during the Kirby–Bauer disc diffusion detection. This result indicates that the integration of heteropolyanions and GT exhibits synergistic effects on the antibacterial activity, which paves a new way to design low-cost antibacterial compound by the introduction of POMs.

Determination of Gatifloxacin or Fleroxacin in Water Sample by Ultrasound-Assisted Ionic Liquid Liquid-Phase Microextraction Coupled with High Performance Liquid Chromatography

Determination of Gatifloxacin or Fleroxacin in Water Sample by Ultrasound-Assisted Ionic Liquid Liquid-Phase Microextraction Coupled with High Performance Liquid Chromatography

Fluoroquinolone resistance and active drug efflux in Enterococci

Objective To investigate the effect of reserpine,an efflux pumps inhibitor, on the activities of fluoroquinolones (FQNs) against Enterococci，and the distribution of efflux pump genes emeA and its correlation with the resistance of Enterococci. To elucidate the relationship between FQN resistance in Enterococci and active efflux. Methods One hundred isolates of enterococci were identified by VITEK microbe automatic system. The antibacterial agent susceptibility tests were performed by the disc diffusion method (K-B) in accordance with the CLSI standards.The minimum inhibitory concentration (MIC) of each FQN was tested by the agar dilution method,and the MIC changes were detected after adding reserpine.The distribution of emeA in 100 isolates of Enterococci was determined by PCR.The χ2 test was used to compare the differences of statistical results. Results After reserpine was used,three-FQN resistance in Enterococci was reduced. Ciprofloxacin,gatifloxacin and levofloxacin resistance was reduced from 42%（42/100） to 28%（28/100）, from 30%（30/100） to 17%（17/100）,and from 33%（33/100） to 23%（23/100）,respectively.The positive rate of emeA gene in 100 strains of Enterococci was 55%（55/100）.There were 45 positive strains(72.6%) in 62 E.faecalis and 10 positive strains(26.4%) in 38 E.faecium.The positive rate of emeA gene in the resistant strains against ciprofloxacin,gatifloxacin and levofloxacin was 73.8%（31/42）,76.7%（23/30）,75.8%（25/33）,respectively ,and the positive rate of emeA gene in the susceptible strains against above 3 antibacterials were 41.4%（24/58）,45.7%（32/70）,44.8%（30/67）. Efflux pump genes emeA in resistant strains is higher than the sensitive strains, with the statistically significant difference(χ2=13.02,8.13 and 8.57，P<0.005). Conclusions Reserpine could inhibit the active efflux of in FQN Enterococci and reduce the MIC for drug-resistant strains in vitro.Multidrug-resistant efflux pump gene emeA was relevant to antimicrobial drug resistance in Enterococci.（Chin J Lab Med,2014,37: 298-301） Key words: Enterococcus; Reserpine; Bacterial proteins

Preparation and characterization of molecularly imprinted poly(hydroxyethyl methacrylate) microspheres for sustained release of gatifloxacin

Molecularly imprinted poly(hydroxyethyl methacrylate) microspheres (PHEMA MIPMs) were prepared via precipitation polymerization in this article, using gatifloxacin (GFLX), hydroxyethyl methacrylate (HEMA), and ethylene glycol dimethacrylate (EGDMA) as template molecule, functional monomer and cross-linker, respectively. The effects of reaction medium, initial total monomers, cross-linker and molecular imprinting on the polymerization were investigated systematically. The interaction between GFLX and HEMA in pre-solution was studied by UV-Visible spectrophotometer, both size and morphology of products were characterized by a scanning electron microscope. When the total initial monomer concentration was 1 vol%, EGDMA content was 70 mol%, a group of uniform PHEMA MIPMs were prepared at different GFLX/MAA molar ratios, with diameter range from 2.06 ± 0.07 to 2.82 ± 0.20 μm. The results of drug loading and in vitro release experiments demonstrated that PHEMA MIPMs could achieve a higher GFLX loading content and a more acceptable sustained release than non-imprinted ones.

Poly(methacrylic acid) microparticles coated with nanolayered chitosan and carbon nanotubes via electrostatic self-assembly for gatifloxacin delivery

A novel poly(methacrylic acid) (PMAA) microcarriers coated with nanolayered chitosan(Cs) and carboxyl modified multi-walled carbon nanotubes (MWCNTs-COOH) via self-assembly method, has been successfully prepared for better loading and sustained release of gatifloxacin (GFLX). Due to the multi-loading and gradient release properties, PMAA/Cs/CNTs could adsorb a great amount of drug (84.89±9.63μgmg−1), and 64.74±2.78% of its loading could slowly release in 24h, which is important to delivery GFLX effectively and to reduce the risk of side effects.

Determination of gatifloxacin in drug formulations, human urine, and serum samples using energy transfer chemiluminescence coupled with flow-injection analysis

A simple and sensitive method for the determination of gatifloxacin (GFLX) is developed by using flow injection analysis with potassium permanganate-sodium sulfite chemiluminescence (CL) detection based on the energy transfer from GFLX to terbium(III). Intense signal instead of the weak CL produced by potassium permanganate-sulfite-GFLX system can be observed when Tb(III) is added to the system. A narrow and intense emission band at 545 nm arising from the excited-state Tb(III) was obtained. Under the optimum conditions, a linear range was 5.0 × 10−8 to 8.0 × 10−6 M and the detection limit was 3.2 × 10−9 M. The method has been successfully applied to the determination of gatifloxacin in drug formulations, urine and serum samples. There was no interference from some common excipients used in pharmaceutical preparations. The possible energy transfer mechanisms in the lanthanide complexes were discussed.

Characterization of the interactions of human serum albumin (HSA), gatifloxacin, and metronidazole using spectroscopic and electrochemical methods

Human serum albumin (HSA), the most abundant protein in blood plasma, is an important carrier for many drugs. Understanding HSA-drug interactions is critical in being able to interpret the distribution and acting mechanisms of these drugs, which is particularly important in the case of multi-drug therapy. In this study, we investigated the interactions between HSA and two commonly used antibiotics, gatifloxacin (GFLX) and metronidazole (MET), in Tris–HCl buffer solution (pH=7.4). The efficacy of the individual drugs (GFLX or MET) and the efficacy of a combination of GFLX and MET were measured using fluorescence spectroscopy, UV absorption spectroscopy, and electrochemical methods. Our results demonstrated that GFLX and MET have a synergistic effect. Briefly, one drug decreased the binding stability with HSA of the other drug, thus increasing the concentration of free drug at the action sites. The interaction of drugs with HSA is a process of complex-formation static quenching. There is approximately one binding site between HSA and the drug (GFLX or MET). The binding distance, r, between the drug and HSA was determined on the basis of the theory of Forster-type non-radiative energy transfer. It was shown that the interaction between the two drugs increased the r-value. Using thermodynamic parameters, we found that the binding of drug-HSA interactions is mainly controlled by electrostatic force. Analysis of the synchronous fluorescence spectrum suggested that the interactions between the drugs have important effects on protein conformation. In conclusion, combining GFLX and MET enhances treatment efficacy. Our study provides a basis to understand the mechanism of the interaction of MET, GFLX and HSA in the human body.

Kinetic spectrophotometric method for the determination of some fourth generation fluoroquinolones in bulk and in pharmaceutical formulations

A kinetic spectrophotometric method for accurate and sensitive determination of gemifloxacin (GMFX) and gatifloxacin (GTFX) has been described. The method is based on the reaction of the studied drugs with potassium permanganate in the presence of sodium hydroxide to form a water-soluble green product which shows maximum absorbance at 604nm. The determination of GMFX and GTFX drugs by rate constant, fixed-concentration, and fixed time methods was feasible with the calibration equations obtained but the fixed time method had been found to be more applicable. The concentration of the selected drugs is calculated using the calibration equation for the fixed time method. The absorbance–concentration plot is linear over the range of 4–36μgmL−1 and 4–40μgmL−1 with correlation coefficient of 0.9998 and 0.9991, for GMFX and GTFX, respectively. The molar absorptivity, Sandell sensitivity, detection and quantification limits were also calculated. The different experimental parameters affecting the development and stability of the color were carefully studied and optimized. The intra- and inter-day RSD values indicated the ruggedness of the method. The proposed method has been successfully applied to pharmaceutical formulations of each drug. Statistical comparison of the results with a well established reported method showed excellent agreement and proved that there is no significant difference in the accuracy and precision.

Development of a Precolumn Derivatization Procedure Prior to Ultrasound-Assisted Cloud Point Extraction for Sensitive Determination of Fluoroquinolones in Eggs by High-Performance Liquid Chromatography with Fluorescence Detection

In this work, a 4-chloro-7-nitrobenzodioxazole (NBD-Cl) derivatization coupled with the ultrasound-assisted cloud point extraction (UACPE) method prior to high-performance liquid chromatography with fluorescence detection (HPLC-FLD) analysis was developed for the determination of four widely used fluoroquinolones (FQs) including norfloxacin (NOR), ciprofloxacin (CIP), sarafloxacin (SAR), and gatifloxacin (GAT) in eggs. The derivatives of FQs with NBD-Cl were extracted into the Triton X-114 surfactant-rich phase, which was analyzed by reversed-phase HPLC-FLD. Ultrasound was applied to accelerate the phase separation in extraction and enhance the extraction efficiency of target analytes. Variable parameters affecting the derivatization and UACPE procedure were systematically evaluated and optimized. Under the optimum conditions, four FQs were successfully separated within 30 min through an Agilent TC-C18 column. Good recoveries of 86.2–103.5 %, which were calculated using a range of spiked samples at three concentrations, were obtained by UACPE. The calibration graphs were linear over the range of 1.2–73.0 μg kg−1 for four FQs with correlation coefficients (R) no less than 0.9957. The limits of detection were 0.2, 0.5, 0.3, and 0.4 μg kg−1 for NOR, CIP, SAR, and GAT, respectively. The precisions indicated by relative standard deviations ranged from 0.6 to 4.3 % for both intraday and interday analysis. The proposed method proved to be a selective, sensitive, and eco-friendly approach which was successfully applied to analyze FQs in eggs at the local farmers market, and none of the target analytes were detected in these samples.

Preparation and characterization of a hydrogel carrier to deliver gatifloxacin and its application as a therapeutic contact lens for bacterial keratitis therapy

A soft and biocompatible hydrogel exhibiting a higher loading and the sustained release of gatifloxacin (GFLX) was developed as the potential matrix to fabricate a therapeutic contact lens for curing bacterial keratitis. 2-hydroxyethyl methacrylate (HEMA) and five other kinds of vinyl monomers with different side groups were used as co-monomers. Copolymerization took place in a cornea shaped mould via the gradient temperature-elevating method. The results of drug loading and in vitro release experiments showed that P(HEMA-co-MAA) achieved the highest drug loading of 11.78±0.77 µg mg−1 among the obtained hydrogels, as well as a slow release. In addition, its physical properties and cytocompatibility were also proved suitable and safe for wearing on the eye surface. In animal experiments, a rat model of bacterial keratitis was established and employed to evaluate the clinical results of certain treatments employing obtained hydrogels; saline and GFLX eye drops were used as negative and positive controls, respectively. Corneal abscess and opacity caused by epithelial erosion and stromal ulceration were almost healed after wearing the drug loaded P(HEMA-co-MAA) hydrogel for 48 h. Its excellent antibacterial effect was also confirmed by testing the bacterial activity in tear extraction via the streak line method.

Development of novel amphiphilic magnetic molecularly imprinted polymers compatible with biological fluids for solid phase extraction and physicochemical behavior study

In the present work, a novel amphiphilic magnetic molecularly imprinted polymer (M-MIP) has been synthesized by a simple non covalent method for the loading of gatifloxacin (GTFX) in polar solvent. This nanomaterial used as sorbent has been applied to the solid phase extraction of GTFX in different spiked biological fluids. For the first time, studies of dispersibility and solubility behaviors with different solvents and water were performed to demonstrate amphiphilicity and also to find the better nanomaterial obtained. Fourier transform infrared (FT-IR), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and X-ray (XRD) were used to characterize the nanomaterials, and Scatchard plot analysis to demonstrate the binding kinetic. Results suggest that the dispersibility, solubility and the adsorption in water have relationships with the structure of nanomaterials prepared. The oleic acid coated on the M-MIP combined with the washing process has enhanced the amphiphilicity of the nanomaterials. The M-MIP2 showed better selectivity and adsorption behavior with imprinted efficiency higher than (2) in water, as well as in biological fluids. Moreover, no interference with constituents of blank urine and blank serum samples for solid phase extraction (SPE) was observed. Moreover, loading recovery was found higher than 95% with low RSD. The novel amphiphilic magnetic nanomaterial prepared here as sorbent is suitable for SPE of GTFX in biological fluids for therapeutic monitoring control. It could be also used as carrier in drug delivery system for experimental and clinical studies.

Combination Effect of Antibiotics Against Bacteria Isolated From Keratitis Using Fractional Inhibitory Concentration Index

To study the in vitro interaction of fluoroquinolones such as levofloxacin (LVFX), gatifloxacin (GFLX), or moxifloxacin (MFLX) in combination with tobramycin (TOB) or cefmenoxime (CMX) against clinical isolates of bacteria from keratitis. The activity of each drug alone was determined by an agar dilution method. Checkerboard synergy testing was then performed against 47 isolates, including Staphylococcus species, Streptococcus species, and Pseudomonas aeruginosa. Antimicrobial combinations were classified as synergistic, additive, indifferent, or antagonistic, according to their fractional inhibitory concentration. The average fractional inhibitory concentration indexes of combined use of LVFX/CMX or GFLX/CMX in Staphylococcus species and Streptococcus species, and LVFX/CMX, GFLX/CMX, MFLX/CMX in gram-negative rods were low. The additive activity of the following drug combinations were seen in more than 70% of isolates: LVFX/CMX and GFLX/CMX against gram-positive cocci and LVFX/CMX, GFLX/CMX, MFLX/CMX against gram-negative rods. No consistent synergistic or antagonistic effect was observed with the combinations used. The combination of LVFX/CMX or GFLX/CMX was predominantly additive for all tested isolates.