Abstract：
Ocular bacterial infections can lead to serious visual disability without proper treatment. Moxifloxacin (MOX) has been approved by the US Food and Drug Administration as a monotherapy for ocular bacterial infections and is available commercially as an ophthalmic solution (0.5% w/v). However, precorneal retention, drainage, and low bioavailability remain the foremost challenges associated with current commercial eyedrops. With this study, we aimed to design a MOX-loaded nanoemulsion (NE; MOX-NE) with mucoadhesive agents (MOX-NEM) to sustain MOX release, as well as to overcome the potential drawbacks of the current commercial ophthalmic formulation. MOX-NE and MOX-NEM formulations were prepared by hot homogenization coupled with probe sonication technique and subsequently characterized. The lead formulations were further evaluated for in vitro release, ex vivo transcorneal permeation, sterilization, and antimicrobial efficacy studies. Commercial MOX ophthalmic solution was used as a control. The lead formulations showed the desired physicochemical properties and viscosity. All lead formulations showed sustained release profiles a period of more than 12 h. Filtered and autoclaved lead formulations were stable for one month (the last time point tested) under refrigeration and at room temperature. Ex vivo transcorneal permeation studies revealed a 2.1-fold improvement in MOX permeation of the lead MOX-NE formulation compared with Vigamox® eyedrops. However, MOX-NEM formulations showed similar flux and permeability coefficients to those of Vigamox® eyedrops. The lead formulations showed similar in vitro antibacterial activity as the commercial eyedrops and crude drug solution. Therefore, MOX-NE and MOX-NEM formulations could serve as effective delivery vehicles for MOX and could improve treatment outcomes in different ocular bacterial infections.
摘要：
如果没有适当的治疗，眼部细菌感染会导致严重的视力障碍。莫西沙星(MOX)已被美国食品和药物管理局批准作为眼部细菌感染的单一疗法,并且可作为眼用溶液(0.5%w/v)商购。然而,角膜前保留,排水,和低生物利用度仍然是与当前商业滴眼液相关的首要挑战。通过这项研究,我们的目的是设计一种负载MOX的纳米乳液（NE;MOX-NE）与粘膜粘着剂（MOX-NEM），以维持MOX的释放，以及克服当前商业眼用制剂的潜在缺点。通过热均质化结合探针超声技术制备MOX-NE和MOX-NEM制剂并随后表征。进一步评估了铅制剂的体外释放，离体角膜渗透，灭菌,和抗菌功效研究。商业MOX眼用溶液用作对照。先导制剂显示出期望的物理化学性质和粘度。所有铅制剂显示持续释放曲线超过12小时。过滤和高压灭菌的铅制剂在冷藏和室温下稳定一个月(最后测试的时间点)。离体经角膜渗透研究显示,与Vigamox®滴眼液相比,前导MOX-NE制剂的MOX渗透改善2.1倍。然而,MOX-NEM制剂显示出与Vigamox®滴眼液相似的通量和渗透系数。先导制剂显示出与商业滴眼液和粗制药物溶液相似的体外抗菌活性。因此,MOX-NE和MOX-NEM制剂可以作为MOX的有效递送载体,并且可以改善不同眼部细菌感染的治疗结果。
