Green method by National Environmental Methods Index and Eco-Scale Assessment for evaluation of gatifloxacin-based product by HPLC.

The literature reveals gaps in the availability of green analytical methods for assessing products containing gatifloxacin (GFX), a fluoroquinolone. Presently, method development is supported by tools such as the National Environmental Methods Index (NEMI) and Eco-Scale Assessment (ESA), which offer objective insights into the environmental friendliness of analytical procedures. The objective of this work was to develop and validate a green method by the NEMI and ESA to quantify GFX in eye drops using HPLC. The method utilized a C8 column (4.6 × 150 mm, 5 µm), with a mobile phase of purified water containing 2% acetic acid and ethanol (70:30, v/v). The injection volume was 10 µL and the flow rate was 0.7 mL/min in isocratic mode at 25°C, with detection performed at 292 nm. The method demonstrated linearity in the range of 2-20 µg/mL, and precision at intra-day (relative standard deviation [RSD] 1.44%), inter-day (RSD 3.45%), and inter-analyst (RSD 2.04%) levels. It was selective regarding the adjuvants of the final product (eye drops) and under forced degradation conditions. The method was accurate (recovery 101.07%) and robust. The retention time for GFX was approximately 3.5 min. The greenness of the method, as evaluated by the NEMI, showed four green quadrants, and by ESA, it achieved a score of 88.

A molecularly imprinted electrochemical sensor with dual functional monomers for selective determination of gatifloxacin.

A molecularly imprinted electrochemical sensor was designed for the selective determination of gatifloxacin (GTX) based on dual functional monomers. Multi-walled carbon nanotube (MWCNT) enhanced the current intensity and zeolitic imidazolate framework 8 (ZIF8) provided a large surface area to produce more imprinted cavities. In the electropolymerization of molecularly imprinted polymer (MIP), p-aminobenzoic acid (p-ABA) and nicotinamide (NA) were used as dual functional monomers, and GTX was the template molecule. Taking [Fe(CN)6]3-/4- as an electrochemical probe, an oxidation peak on the glassy carbon electrode was located at about 0.16 V (vs. saturated calomel electrode). Due to the diverse interactions among p-ABA, NA, and GTX, the MIP-dual sensor exhibited higher specificity towards GTX than MIP-p-ABA and MIP-NA sensors. The sensor had a wide linear range from 1.00 × 10-14 to 1.00 × 10-7 M with a low detection limit of 2.61 × 10-15 M. Satisfactory recovery between 96.5 and 105% with relative standard deviation from 2.4 to 3.7% in real water samples evidenced the potential of the method in antibiotic contaminant determination.

Transcriptome analysis to elucidate the toxicity mechanisms of fenvalerate, sulfide gatifloxacin, and ridomil on the hepatopancreas of Procambarus clarkii.

Most antibiotics, insecticides, and other chemicals used in agricultural and fishery production tend to persist in the environment. Fenvalerate, sulfide gatifloxacin, and ridomil are widely used in aquaculture as antibacterial, antifungal, and antiparasitic drugs; however, their toxicity mechanism remains unclear. Thus, we herein analyzed the effects of these three drugs on the hepatopancreas of Procambarus clarkii at the transcriptome level. Twelve normalized cDNA libraries were constructed using RNA extracted from P. clarkii after treatment with fenvalerate, sulfide gatifloxacin, or ridomil and from an untreated control group, followed by Kyoto Encyclopedia of Genes and Genomes pathway analysis. In the control vs fenvalerate and control vs sulfide gatifloxacin groups, 14 and seven pathways were significantly enriched, respectively. Further, the effects of fenvalerate and sulfide gatifloxacin were similar on the hepatopancreas of P. clarkii. We also found that the expression level of genes encoding senescence marker protein-30 and arylsulfatase A was downregulated in the sulfide gatifloxacin group, indicating that sulfide gatifloxacin accelerated the apoptosis of hepatopancreatocytes. The expression level of major facilitator superfamily domain containing 10 was downregulated, implying that it interferes with the ability of the hepatopancreas to metabolize drugs. Interestingly, we found that Niemann pick type C1 and glucosylceramidase-ß potentially interact with each other, consequently decreasing the antioxidant capacity of P. clarkii hepatopancreas. In the fenvalerate group, the downregulation of the expression level of xanthine dehydrogenase indicated that fenvalerate affected the immune system of P. clarkii; moreover, the upregulation of the expression level of pancreatitis-associated protein-2 and cathepsin C indicated that fenvalerate caused possible inflammatory pathological injury to P. clarkii hepatopancreas. In the ridomil group, no pathway was significantly enriched. In total, 21 genes showed significant differences in all three groups. To conclude, although there appears to be some overlap in the toxicity mechanisms of fenvalerate, sulfide gatifloxacin, and ridomil, further studies are warranted.

A systems toxicology approach to explore toxicological mechanisms of fluoroquinolones-induced testis injury.

The widespread use of fluoroquinolones (FQs) causes a serious risk to the environment and human health. Here, we evaluated the potential effect to induce testis damage by gatifloxacin (GAT) intragastrically treatment in mice (25, 50, and 100 mg/kg body weight per day for 7 days). We observed testicular weight, serum testosterone, antioxidant enzyme activity, and mRNA levels and pathways. Testicular histopathology indicated that GAT administration induced a dose-dependent spermatogenesis abnormality. At 50 mg/kg, GAT altered gene expression but did not change the weight and the levels of testosterone and antioxidant enzymes. These findings indicate that mRNA levels are more sensitive than weight and testosterone for detecting GAT testicular toxicity. We also found that GAT induced testicular damage by regulating the candidate genes associated with spermatogenesis, germ cell movement, testicular fibrosis, and reproductive axis development. This study enhances our perception of the mechanism of FQs-induced testicular toxicity and environmental effects. However, the molecular mechanism needs to be further researched.

An adjusted 3D-QSAR model for the combined activity of fluoroquinolones photodegradation and microbial degradation assisted by dynamic simulation and its application in molecular modification.

This study developed a comprehensive characterization method for the combined degradation effect of modified fluoroquinolones (FQs) photodegradation and microbial degradation. A combination of revised 3D-QSAR model, molecular docking, path simulation inference, pharmacokinetics, molecular dynamics (MD) simulation and toxicokinetics simulation was used to construct a systematic environment-friendly drug screening system. Five derivatives were screened with significantly improved combined degradation effect (over 20%) and functional characteristics and human health parameters through combined model verification, functional and human health risk assessment. The simulation path of photo- and microbial-degradation of gatifloxacin and new gatifloxacin molecules was derived, and the reaction energy barrier was also calculated. The ratio of the total rate-determining steps change rate of the decreased energy barrier (14.10%:26.30%) was consistent with the ratio of the increased degradation performance predicted by the model (22.87%:19.77%), demonstrating the reliability of revised 3D-QSAR model and it could be applied in molecular modification. MD and toxicokinetics simulation were used to predict the binding energy and aquatic toxicity between photo- and microbial-degradation products and the degradation enzymes, which further to screen the degradation pathways with low potential environmental risks. The findings will be helpful to screen environment-friendly drug and develop appropriate strategies for its risk management.

Dissipation Dynamics of Doxycycline and Gatifloxacin and Accumulation of Heavy Metals during Broiler Manure Aerobic Composting.

In this study, broilers were fed with heavy-metal-containing diets (Zn, Cu, Pb, Cr, As, Hg) at three rates (T1: 5 kg premix/ton feed, T2: 10 kg premix/ton feed and T3: 15 kg premix/ton feed) and Doxycycline (DOX) and Gatifloxacin (GAT) at low or high doses (T4: 31.2 mg DOX/bird/day and 78 mg GAT/bird/day, T5: 15.6 mg DOX/bird/day and 48 mg GAT/bird/day) to assess the accumulation of various heavy metals and the fate of two antibiotics in broiler manure after 35 days of aerobic composting. The results indicated that the two antibiotics changed quite differently during aerobic composting. About 14.96-15.84% of Doxycycline still remained at the end of composting, while Gatifloxacin was almost completely removed within 10 days of composting. The half-lives of Doxycycline were 13.75 and 15.86 days, while the half-lives of Gatifloxacin were only 1.32 and 1.38 days. Based on the Redundancy analysis (RDA), the concentration of antibiotics was significantly influenced by physico-chemical properties (mainly temperature and pH) throughout the composting process. Throughout the composting process, all heavy metal elements remained concentrated in organic fertilizer. In this study the Cr content reached 160.16 mg/kg, 223.98 mg/kg and 248.02 mg/kg with increasing premix feed rates, similar to Zn, which reached 258.2 mg/kg, 312.21 mg/kg and 333.68 mg/kg. Zn and Cr concentrations well exceeded the United States and the European soil requirements. This experiment showed that antibiotic residues and the accumulation of heavy metals may lead to soil contamination and pose a risk to the soil ecosystem.

Stepwise optimization and sensitivity improvement of green micellar electrokinetic chromatography method to simultaneously determine some fluoroquinolones and glucocorticoids present in various binary ophthalmic formulations.

A sensitive micellar electrokinetic chromatography method is presented to simultaneously quantify ofloxacin, gatifloxacin, dexamethasone sodium phosphate and prednisolone acetate. The method has the advantages of being rapid, accurate, reproducible, ecologically acceptable and sensitive. The electrophoretic separation utilized 20 mm borate buffer as background electrolyte with pH 10.0 ± 0.1 and 50 mm sodium dodecyl sulfate as a micelle forming molecule. A capillary tube (50 µm i.d., 33 cm) of fused silica was used and on-column diode array detection at 243 nm for dexamethasone sodium phosphate and prednisolone acetate, and 290 nm for ofloxacin and gatifloxacin. Various factors were optimized such as the background electrolyte (type, concentration and pH), addition of sodium dodecyl sulfate and its concentration, detection wavelength, applied voltage and injection parameters. The studied drugs were efficiently separated in 6.2 min, at 20 kV with high resolution. The greenness of the method was estimated using an eco-scale tool and the presented method was found to have excellent green characteristics. The method was validated in conformance with International Conference on Harmonization guidelines, with acceptable accuracy, precision and selectivity. The suggested method can be employed for the economic analysis of the four drugs in dissimilar binary combinations of eye drops saving solvents and chemicals.

Evaluating the in vitro efficacy of gatifloxacin, levofloxacin and gentamicin against Acanthamoeba cysts.

PURPOSE: To evaluate the in vitro efficacy of three commercial ophthalmic solutions (gatifloxacin, levofloxacin and gentamicin) against cysts of Acanthamoeba species. DESIGN: Experimental study METHODS: Acanthamoeba cysts belonging to genotypes T3, T4 and T5 were incubated with three ophthalmic solutions for different periods of time; 1, 24, 48 and 72 h at 37 °C. After incubation, treated cysts were stained with trypan blue and counted to express the percent of growth inhibition. Additionally, the viability of treated cysts was assessed by culturing them in PYG medium at 30 °C for 72 h as well as on non-nutrient agar plates at 30 °C for 1 month. RESULTS: Acanthamoeba cysts of all genotypes were susceptible to gentamicin and gatifloxacin after exposure for 1 h and 24 h, respectively, and for levofloxacin, cysts of all genotypes were resistant to levofloxacin even after 72 h of incubation. Gentamicin and gatifloxacin showed statistically highly significant difference (P < 0.001), and levofloxacin showed statistically significant difference (P < 0.05) in comparison to non-treated control. CONCLUSIONS: Gentamicin and gatifloxacin were highly effective against Acanthamoeba cysts. Although our results should be confirmed in animal models, this result will guide the choice of the appropriate ophthalmic drugs for early treatment of eye infection caused by Acanthamoeba spp.

Gatifloxacin-1,2,3-triazole-isatin hybrids and their antimycobacterial activities.

A series of gatifloxacin-1,2,3-triazole-isatin hybrids 8a-l were designed, synthesized, and screened for their in vitro antimycobacterial activity as well as cytotoxicity toward Chinese Hamster Ovary (CHO) cells. The synthesized hybrids showed considerable activity against MTB H37 Rv and two MDR-MTB strains with minimal inhibitory concentration (MIC) of 0.25-8 µg/ml, and the hybrid 8a (MICMTB H37Rv : 0.25 µg/ml and MICMDR-MTB : 0.5 and 1 µg/ml) was found to be most active against the tested strains, which was not inferior to the parent gatifloxacin (MIC: 0.5, 0.25, and 0.5 µg/ml) against all three tested strains, and was ≥128-fold more active than isoniazid (MIC: ≥64 µg/ml) and rifampicin (MIC: >128 µg/ml) against the two MDR-MTB strains. Moreover, hybrid 8a (CC50 : 8.0 µg/ml) also displayed acceptable cytotoxicity toward CHO cells, and the selectivity index was 32. The structure-activity relationship and structure-cytotoxicity relationship were also enriched.

Potential Active Targeting of Gatifloxacin to Macrophages by Means of Surface-Modified PLGA Microparticles Destined to Treat Tuberculosis.

Tuberculosis (TB) is an infectious disease caused by Mycobacterium tuberculosis and represents one of the leading causes of mortality worldwide due to multidrug-resistant TB (MDR-TB). In our work, a new formulation of biodegradable PLGA microparticles was developed for pulmonary administration of gatifloxacin, using a surface modifier agent to actively target alveolar macrophages thereby allowing to gain access of the drug to Mycobacterium tuberculosis. For this, rapid uptake of the particles by macrophages is beneficial. This process was evaluated with fluorescein-loaded microparticles using PLGA 502 or PLGA 502H as polymers and labrafil as surface modifier. Cell phagocytosis was studied in raw 264.7 mouse macrophage cell line after 3, 5, 24, and 48 h incubation with the microparticles. Labrafil enhanced the uptake rate of PLGA 502H microparticles by macrophages which was directly related to the modification of the polymer matrix. Gatifloxacin-loaded PLGA microparticles using PLGA 502 or PLGA 502H and labrafil were prepared. From our results, only microparticles prepared with PLGA 502H and labrafil exhibited high encapsulation efficiency (89.6 ± 0.2%), rapid phagocytosis by macrophages (3 h), and remained inside the cells for at least 48 h, thereby resulting in a suitable carrier to potentially treat MDR-TB.

[Comparison of the permeability between the rabbit cornea and sclera ex vivo].

Objective: Comparison of the permeability between the rabbit cornea and sclera ex vivo by determining the concentration of gatifloxacin using LC-MS/MS method, which may provide the basis for a new route of drug administration. Methods: Experimental study. The permeability of the cornea and sclera in healthy male New Zealand rabbits was evaluated by using Franz diffusion pool. We chose both gatifloxacin ophthalmic solution and gel as the test drugs, and calculated the cumulative permeation amounts (Qn), apparent permeability coefficient(P(app)). Results: The linear range of gatifloxacin was 5-1 000 ng/ml. The intra-day and inter-day precision was 1.7% -2.8% and 1.0% - 2.3%. Q(n) and P(app) of gatifloxacin ophthalmic solution in cornea and sclera ex vivo were 177.57, 517.52 µg/cm(2) and 4.34, 12.51 cm/s respectively, whereas that of gatifloxacin ophthalmic gel were 151.87, 411.05 µg/cm(2) and 3.66, 9.21 cm/s. Conclusion: This validated method could be applied to determine the gatifloxacin. The cumulative permeation amounts and apparent permeability coefficient of sclera are significantly higher than that of cornea for both ophthalmic solution and gel, suggesting that the development of a new route of drug administration based on sclera may have potential advantage. (Chin J Ophthalmol, 2019, 55: 928-932).

High-performance liquid chromatography study of gatifloxacin and sparfloxacin using erythrosine as post-column resonance Rayleigh scattering reagent and mechanism study.

Herein, a highly selective high-performance liquid chromatography (HPLC) coupled with resonance Rayleigh scattering (RRS) method was developed to detect gatifloxacin (GFLX) and sparfloxacin (SPLX). GFLX and SPLX were first separated by HPLC, then, in pH 4.4 Britton-Robinson (BR) buffer medium, protonic quaternary ammonia cation of GFLX and SPLX reacted with erythrosine (ERY) to form 1:1 ion-association complexes, which resulted in a significant enhancement of RRS signal. The experimental conditions of HPLC and post-column RRS have been investigated, including detection wavelength, flow rate, pH, reacting tube length and reaction temperature. Reaction mechanism were studied in detail by calculating the distribution fraction. The maximum RRS signals for GFLX and SPLX were recorded at λex  = λem  = 330 nm. The detection limits were 3.8 ng ml-1 for GFLX and 17.5 ng ml-1 for SPLX at a signal-to-noise ratio of 3. The developed method was successfully applied to the determination of GFLX and SPLX in water samples. Recoveries from spiked water samples were 97.56-98.85%.

Design and characterization of multifaceted lyophilized liposomal wafers with promising wound healing potential.

Various dressings are available to heal chronic wounds which many times fail to achieve the expected results. To overcome some of their drawbacks, formulation of a novel dressing; lyophilized liposomal wafers having better wound healing potential has been proposed in the present study. The drug incorporated in the formulation is gatifloxacin (GTX) which is a fourth-generation fluoroquinolone antibiotic having in vitro activity against both Gram-negative and Gram-positive bacteria. The formulation was designed in three stages where at first liposomes were prepared, the liposomes were converted to gel using chitosan and lastly this gel was lyophilized to form liposomal wafers. Liposomes were prepared by varying the concentration of lipid and cholesterol and evaluated for particle size, entrapment efficiency, in vitro cumulative release, transmission electron microscopy (TEM) and scanning electron microscopy (SEM). Liposomes were converted to liposomal gel using chitosan and evaluated for texture, clarity, viscosity, spreadibility and in vitro drug release. Finally, this liposomal batch was subjected to lyophilization to convert it to liposomal wafers and subjected to SEM, differential scanning calorimetric, X-ray diffraction and drug release studies. The in vivo studies were carried out on Wistar rats where wound healing potential of the wafers was confirmed by histopathological evaluation.

Highly Stable Zr(IV)-Based Porphyrinic Metal-Organic Frameworks as an Adsorbent for the Effective Removal of Gatifloxacin from Aqueous Solution.

Water stable Zr-metal−organic framework nanoparticles (PCN-224 NPs, PCN refers to porous coordination network) have been solvothermally synthesized. PCN-224 NPs show spherical shape with smooth surface and particle size of approximately 200 nm. PCN-224 NPs can be stable in acid and aqueous solutions, as confirmed by powder X-ray diffraction. Gatifloxacin (GTF) adsorption measurements showed that PCN-224 NPs exhibit a high adsorption capacity of 876 mg·g−1. Meanwhile, the adsorption factors, adsorption characteristics, and mechanisms of GTF were investigated in batch adsorption experiments.

Effects on the QT Interval of a Gatifloxacin-Containing Regimen versus Standard Treatment of Pulmonary Tuberculosis.

The effects on ventricular repolarization-recorded on the electrocardiogram (ECG) as lengthening of the QT interval-of acute tuberculosis and those of standard and alternative antituberculosis regimens are underdocumented. A correction factor (QTc) is introduced to make the QT independent of the heart rate, translating into the slope of the regression line between QT and heart rate being close to zero. ECGs were performed predosing and 1 to 5 h postdosing (month 1, month 2, and end of treatment) around drugs' peak concentration time in tuberculosis patients treated with either the standard 6-month treatment (rifampin and isoniazid for 6 months and pyrazinamide and ethambutol for 2 months; "control") or a test regimen with gatifloxacin, rifampin, and isoniazid given for 4 months (pyrazinamide for the first 2 months) as part of the OFLOTUB study, a randomized controlled trial conducted in five African countries. Drug levels were measured at steady state (month 1) in a subset of patients. We compared treatment effects on the QTc and modeled the effect of individual drugs' maximum concentrations of drug in serum (Cmax) on the Fridericia-corrected QT interval. A total of 1,686 patients were eligible for the correction factor analysis of QT at baseline (mean age, 30.7 years; 27% female). Median heart rate decreased from 96/min at baseline to 71/min at end of treatment, and body temperature decreased from 37.2 to 36.5°C. Pretreatment, the nonlinear model estimated the best correction factor at 0.4081 in between Bazett's (0.5) and Fridericia's (0.33) corrections. On treatment, Fridericia (QTcF) was the best correction factor. A total of 1,602 patients contributed to the analysis of QTcF by treatment arm. The peak QTcF value during follow-up was >480 ms for 21 patients (7 and 14 in the test and control arms, respectively) and >500 ms for 9 patients (5 and 4, respectively), corresponding to a risk difference of -0.9% (95% confidence interval [CI], -2.0% to 2.3%; P = 0.12) and 0.1% (95% CI, -0.6% to 0.9%; P = 0.75), respectively, between the test and control arms. One hundred six (6.6%) patients had a peak measurement change from baseline of >60 ms (adjusted between-arm difference, 0.8%; 95% CI, -1.4% to 3.1%; P = 0.47). No evidence was found of an association between Cmax of the antituberculosis drugs 1 month into treatment and the length of QTcF. Neither a standard 6-month nor a 4-month gatifloxacin-based regimen appears to carry a sizable risk of QT prolongation in patients with newly diagnosed pulmonary tuberculosis. This is to date the largest data set studying the effects of antituberculosis regimens on the QT, both for the standard regimen and for a fluoroquinolone-containing regimen. (This study has been registered at ClinicalTrials.gov under identifier NCT00216385.).

Design, synthesis and in vitro anti-mycobacterial evaluation of gatifloxacin-1H-1,2,3-triazole-isatin hybrids.

A set of novel gatifloxacin-1H-1,2,3-triazole-isatin hybrids 6a-l was designed, synthesized and evaluated for their in vitro anti-mycobacterial activities against M. tuberculosis (MTB) H37Rv and MDR-TB as well as cytotoxicity. The results showed that all the targets (MIC: 0.025-3.12µg/mL) exhibited excellent inhibitory activity against MTB H37Rv and MDR-TB, but were much more toxic (CC50: 7.8-62.5µg/mL) than the parent gatifloxacin (GTFX) (CC50: 125µg/mL). Among them, 61 (MIC: 0.025µg/mL) was 2-32 times more potent in vitro than the references INH (MIC: 0.05µg/mL), GTFX (MIC: 0.78µg/mL) and RIF (MIC: 0.39µg/mL) against MTB H37Rv. The most active conjugate 6k (MIC: 0.06µg/mL) was 16->2048 times more potent than the three references (MIC: 1.0->128µg/mL) against MDR-TB. Both of the two hybrids warrant further investigations.

Characterization of melt-quenched and milled amorphous solids of gatifloxacin.

The objectives of this study were to characterize and investigate the differences in amorphous states of gatifloxacin. We prepared two types of gatifloxacin amorphous solids coded as M and MQ using milling and melt-quenching methods, respectively. The amorphous solids were characterized via X-ray diffraction (XRD), nonisothermal differential scanning calorimetry (DSC) and time-resolved near-infrared (NIR) spectroscopy. Both the solids displayed halo XRD patterns, the characteristic of amorphous solids; however, in the non-isothermal DSC profiles, these amorphous solids were distinguished by their crystallization and melting temperatures. The Kissinger-Akahira-Sunose plots of non-isothermal crystallization temperatures at various heating rates indicated a lower activation energy of crystallization for the amorphous solid M than that of MQ. These results support the differentiation between two amorphous states with different physical and chemical properties.

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

Composites of gatifloxacin (GFLX)-loaded poly (lactic-co-glycolic) acid (PLGA) and ß-tricalcium phosphate (ßTCP) 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.

The effect of gatifloxacin 0.3% or moxifloxacin 0.5% on corneal healing, ocular tolerability and toxicity following pterygium surgery.

PURPOSE: To compare the rate of corneal epithelial healing and ocular tolerability following pterygium surgery between gatifloxacin and moxifloxacin. METHODS: In this double masked, prospective, controlled study 40 patients were randomized to receive prophylactic topical gatifloxacin 0.3% or moxifloxacin 0.5% following pterygium surgery. Patients were examined on days 1, 3, 7 and 21 post-operatively or until complete corneal epithelial healing. The primary outcome measure was the area of corneal epithelial defect during the post-operative period. Patients graded post-operative ocular pain, foreign body sensation, tearing, general burning sensation and burning sensation post-antibiotic drops instillation on a scale of 1-5. Conjunctival hyperemia and superficial punctate keratopathy (SPK) were measured on a scale of 0-3. RESULTS: No significant differences between groups were found in terms of corneal epithelial defect percentage over time (p = 0.989) and there was no significant difference between groups on each of the post-operative days. No significant differences were noted in terms of post-operative ocular pain, foreign body sensation, tearing, general burning sensation, burning sensation post-antibiotic drops instillation, conjunctival hyperemia and SPK. CONCLUSIONS: Gatifloxacin and moxifloxacin showed equivalent results in terms of corneal epithelial healing and ocular tolerability following pterygium surgery. This study suggests that there was no apparent added epithelial toxicity due to the presence of benzalkonium chloride in the gatifloxacin preparation when compared to moxifloxacin.

Development of gatifloxacin-loaded cationic polymeric nanoparticles for ocular drug delivery.

The present investigation aimed at improving the ocular bioavailability of gatifloxacin by prolonging its residence time in the eye and reducing problems associated with the drug re-crystallization after application through incorporation into cationic polymeric nanoparticles. Gatifloxacin-loaded nanoparticles were prepared via the nanoprecipitation and double emulsion techniques. A 50:50 Eudragit® RL and RS mixture was used as cationic polymer with other formulation parameters varied. Prepared nanoparticles were evaluated for size, zeta potential, and drug loading. An optimized formulation was selected and further characterized for in vitro drug release, cytotoxicity, and antimicrobial activity. The double emulsion method produced larger nanoparticles than the nanoprecipitation method (410 nm and 68 nm, respectively). Surfactant choice also affected particle size and zeta potential with Tween 80 producing smaller-sized particles with higher zeta potential than PVA. However, the zeta potential was positive at all experimental conditions investigated. The optimal formulation produced by double emulsion technique and has achieved 46% drug loading. This formulation had optimal physicochemical properties with acceptable cytotoxicity results, and very prolonged release rate. The particles antimicrobial activities of the selected formulation have been tested against Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus and showed prolonged antimicrobial effect for gatifloxacin.