Novel nanostructured lipid carrier-based inserts for controlled ocular drug delivery: evaluation of corneal bioavailability and treatment efficacy in bacterial keratitis

Objectives: The aim of the present study was to develop novel ofloxacin (OFX)-loaded nanostructured lipid carrier (NLC)-based inserts for ocular application for treatment of bacterial keratitis.

Methods: NLC loaded with 0.3% OFX was prepared by means of high shear homogenization and 0.75% chitosan oligosaccharide lactate (COL) was added. Glycerin or PEG 400 at the range of 1 – 15% was added to NLCs as plasticizers and inserts were developed by solvent casting evaporation. Characterization, in vitro release, microbiological, ex vivo and in vivo studies were performed.

Results: The inserts developed with the addition of glycerin (Ins3_OFX) was found as optimal. The kinetic studies revealed that the release of Ins3_OFX was a combination of diffusion and swelling. Ins3_OFX was more bioadhesive in texture profile analysis studies. In the in vivo studies performed with rabbits, the pre-ocular retention time was enhanced up to 24 h and C_max was increased almost six times in comparison with commercial. The rabbits were infected with Staphylococcus aureus and keratitis was confirmed. This group was treated with Ins3_OFX and they recovered in 7 days with no significant sign of conjunctival redness and corneal opacity.

Conclusion: NLC-based inserts developed with COL and glycerin may be offered as appropriate vehicles for ocular delivery.     

Production and application of a monoclonal antibody (mAb) against ofloxacin in milk,chicken and pork

A modified N-hydroxysuccinimide (NHS) ester method was employed to successfully synthesise an immunogen of ofloxacin (OFLX) that was used to induce immune response and thus be able to produce anti-OFLX monoclonal antibodies (mAbs). The prepared anti-OFLX mAb was found to be very specific, sensitive and of high affinity during application. The mAb showed high sensitivity with the half maximal inhibitory concentration (IC₅₀), limit of detection (LOD) and detection range (IC₂₀–IC₈₀) values of 1.17, 0.089 and 0.18?±?0.038?–?7.64?±?1.246?ng?mL^–1, respectively, at an optimal pH of 8.2 and a salt concentration of 0.8%. The intra-assay and inter-assay recoveries from spiked food (cow milk, chicken and pork) samples were 79.38–112.4% and 74.75–108.4% with a precision (%CV) of 1.4–7.5 and 1.2–3.5, respectively. From these results, the icELISA method developed is suitable for future use as a rapid screening method to detect and control the illegal content of OFLX residues in food samples.     

氧氟沙星对映体在经不同诱导剂诱导的大鼠肝微粒体中的葡醛酸化代谢

为评价氧氟沙星（OFLX）对映体葡醛酸化代谢的立体选择性,采用手性HPLC法测定大鼠肝微粒体孵育液中OFLX对映体. 结果显示：经苯巴比妥（PB）和β-萘黄酮（BNF）诱导的不同葡醛酸转移酶（UDPGT）亚族对OFLX对映体葡醛酸化代谢有不同的影响. 在所试验的对照,PB或BNF诱导的微粒体中S-（-）-和R-（+）-OFLX之间,K_m和V_max无显著性差异;但PB组中S- （-）-和R-（+）-OFLX的K_m和V_max与对照组或BNF组相应的对映体比较有显著性差异;OFLX对映体之间的Cl_int在对照组与BNF组没有显著性差异;而在PB组则有显著性差异. 另外BNF组的Cl_int较对照组和PB组分别有显著性差异. 因此,经PB诱导的UDPGT亚族对S-和R-OFLX的Ⅱ相代谢存在立体选择性,并主要是由于其催化部位的差异引起了内在清除率的变化.     

复方氧氟沙星栓剂的制备与质量标准研究

报道了以甘油、明胶、聚乙二醇为基质的复方氧氟沙星阴道栓的制备方法．并制定了质量标准．平均回收率,氧氟沙星为１０１－７％ ,ＲＳＤ 为１－３６ ％ ;甲硝唑为９９－２ ％ ,ＲＳＤ 为０－６ ％ ．     

二种滴耳液治疗中耳炎的疗效比较

目的：观察氧氟沙星滴耳液和氯霉素滴耳液对中耳炎患者的疗效。方法：将84例中耳炎患者（计97只患耳）随机均分为二组,分别用氧氟沙星及氯霉素滴耳液治疗,比较治疗前后症状改善及不良反应。结果：氯霉素总有效率90．48％,氧氟沙星组总有效率92．86％,无统计学差异（P〉0．05）。治疗一周后氯霉素组干耳率80．oo％,氧氟沙星组干耳率96．15％,氧氟沙星组优于氯霉素组（P〈0．01）。氯霉素组不良反应共12例（28．57％）,氧氟沙星组不良反应共5例（11．90％）。结论：氯霉素滴耳液和氧氟沙星滴耳液能有效治疗中耳炎,但氧氟沙星滴耳液促进单纯性化脓性中耳炎的炎性渗出吸收的效果较氯霉素滴耳液好,且不良反应更小。     

RP-HPLC Method for Simultaneous Estimation of Nitazoxanide and Ofloxacin in Tablets

A reverse phase high performance liquid chromatography method was developed for simultaneous estimation of nitazoxanide and ofloxacin in tablet formulation. The separation and quantification was achieved by Hiq Sil C₁₈V Size 4.6 mm Ø ^*250 mm column in isocratic mode, with mobile phase consisting of acetonitrile-methanol-0.4 M citric acid, (60:30:10, v/v/v). Citric acid used to stabilize nitazoxanide and ofloxacin in mobile phase. The mobile phase was pumped at a rate of 0.6 ml/min and the detection was carried out at 304 nm. The retention time of ofloxacin and nitazoxanide was found to be 3.122 and 5.902 min, respectively. The method was validated for linearity, accuracy, and precision. Linearity for ofloxacin and nitazoxanide were in the range 2-36 μg/ml and 5-90 μg/ml, respectively. The developed method was found to be accurate, precise and selective for simultaneous estimation of ofloxacin and nitazoxanide in tablets.     

Ofloxacin: new applications for the prevention of urinary tract infections in renal graft recipients

C. Rafat, S. Vimont, P.Y. Ancel, Y.C. Xu‐Dubois, L. Mesnard, N. Ouali, M. Denis, A. Vandewalle, E. Rondeau, A. Hertig. Ofloxacin: new applications for the prevention of urinary tract infections in renal graft recipients
Transpl Infect Dis 2011: 13: 344–352. All rights reserved Abstract: Background. Urinary tract infections (UTIs), the most common form of bacterial infection in kidney transplant recipients, recently have been demonstrated to be detrimental for long‐term graft outcome. Therefore, reinforcing antibiotic prophylaxis might be vital, in addition to basic hygiene recommendations, surgical care, and prophylaxis by trimethoprim–sulfamethoxazole. Methods. In 2006, a Legionella pneumophila contamination of our department's water pipes meant that all the patients undergoing renal transplantation underwent a 1‐month regimen of ofloxacin (OFLO) (200 mg every other day). We took this opportunity to measure the incidence of UTI, including acute pyelonephritis (APN), in 100 consecutive patients transplanted before (n=50) and after (n=50) this treatment decision was reached. We also studied the antimicrobial resistance profiles in our department and in the rest of the hospital. Results. No patient developed Legionnaire's disease. A dramatic decrease in the incidence of UTI (?63%) was also seen in patients undergoing OFLO treatment. Logistic regression analysis demonstrated that the use of OFLO was independently associated with a reduction in UTI (odd ratio [OR]=0.31%, 95% confidence interval [CI] 0.11–0.84, P=0.02) and APN (OR=0.21%, 95% CI 0.07–0.98, P=0.045). This protection was sustained during the whole first year post transplantation. As for resistance rates, we observed a decrease in the susceptibility of Pseudomonas aeruginosa to ciprofloxacin in our nephrology department, compared with that observed in the rest of the hospital. The incidence of multi‐resistant bacteria was stable. Discussion. Our unintentional extension of prophylactic antibiotherapy with OFLO gave rise to a dramatic decrease in the 1‐year incidence of UTI and APN in kidney recipients. Emergence of resistant strains is, however, a major concern.     

白内障术前滴用氧氟沙星滴眼液对结膜囊细菌培养的影响

目的:观察老年性白内障患者术前应用氧氟沙星滴眼液对结膜囊细菌培养的影响。方法:老年性白内障患者30例60眼,随机分成两组:对照组15例30眼,3g/L氧氟沙星点眼组15例30眼,平均点眼5次,l滴/次。观察点药前,点药l,2,3d,结膜囊内细菌的变化。结果:点药前,点药1,2,3d,结膜囊内细菌落积分的变化:对照组,51,51,33,42;3g/L氧氟沙星点眼组,51,30,9,0。配对t检验统计分析,点药3d,P=0.043。结膜囊内细菌检出率的变化:对照组,60%,60%,40%,50%;3g/L氧氟沙星点眼组,60%,30%,10%,0。χ2检验,点药3d,P<0.01。结论:老年性白内障患者术前应用氧氟沙星滴眼液点眼,3d可以达到结膜囊内无细菌。     

Long-Term Maintenance Antiretroviral Therapy with Saquinavir Hard Gel,After Voluntary Abandonment of Successful Induction HAART

Abstract

HIV-infected patients who voluntarily resorted to an apparently suboptimal drug association including saquinavir hard gel after attaining viral suppression thanks to an antiretroviral regimen based on potent protease inhibitors, had a satisfactory 12-18-month clinical and laboratory outcome. The effects of a potent and sufficiently prolonged induction antiretroviral therapy may be maintained for 12 months or more, especially when the maintenance regimen includes novel nucleoside analogues, and specific genotypical mutations are absent.