Youssef Ahmed Adel Ali, Thakkar Ruchi, Senapati Samir, Joshi Poorva H, Dudhipala Narendar, Majumdar Soumyajit
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, University of Mississippi, Oxford, MS 38677, USA.
Department of Pharmaceutical Technology, Faculty of Pharmacy, Kafrelsheikh University, Kafrelsheikh 33516, Egypt.
Pharmaceutics. 2022 Jun 12;14(6):1246. doi: 10.3390/pharmaceutics14061246.
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% /). 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.
眼部细菌感染若未得到恰当治疗，可能导致严重的视力残疾。莫西沙星（MOX）已获美国食品药品监督管理局批准，可作为眼部细菌感染的单一疗法，且作为眼科溶液（0.5%）在市场上有售。然而，角膜前滞留、引流以及低生物利用度仍是当前市售眼药水面临的首要挑战。通过本研究，我们旨在设计一种含有粘膜粘附剂的载莫西沙星纳米乳剂（NE；MOX-NE）以维持莫西沙星的释放，同时克服当前市售眼科制剂的潜在缺点。通过热均质结合探头超声技术制备了MOX-NE和MOX-NEM制剂，并随后对其进行了表征。对先导制剂进一步进行体外释放、离体角膜渗透、灭菌以及抗菌功效研究。将市售莫西沙星眼科溶液用作对照。先导制剂呈现出所需的物理化学性质和粘度。所有先导制剂均显示出超过12小时的缓释曲线。经过过滤和高压灭菌的先导制剂在冷藏和室温下可稳定保存一个月（测试的最后时间点）。离体角膜渗透研究表明，与Vigamox眼药水相比，先导MOX-NE制剂的莫西沙星渗透率提高了2.1倍。然而，MOX-NEM制剂的通量和渗透系数与Vigamox眼药水相似。先导制剂显示出与市售眼药水和原料药溶液相似的体外抗菌活性。因此，MOX-NE和MOX-NEM制剂可作为莫西沙星的有效给药载体，并可改善不同眼部细菌感染的治疗效果。
