PDF(Pubmed)
Abstract：
Bacterial conjunctivitis (BC) entails inflammation of the ocular mucous membrane. Early effective treatment of BC can prevent the spread of the infection to the intraocular tissues, which could lead to bacterial endophthalmitis or serious visual disability. In 2003, gatifloxacin (GTX) eyedrops were introduced as a new broad-spectrum fluoroquinolone to treat BC. Subsequently, GTX use was extended to other ocular bacterial infections. However, due to precorneal loss and poor ocular bioavailability, frequent administration of the commercial eyedrops is necessary, leading to poor patient compliance. Thus, the goal of the current investigation was to formulate GTX in a lipid-based drug delivery system to overcome the challenges with the existing marketed eyedrops and, thus, improve the management of bacterial conjunctivitis. GTX-NLCs and SLNs were formulated with a hot homogenization-probe sonication method. The lead GTX-NLC formulation was characterized and assessed for in vitro drug release, antimicrobial efficacy (against methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa), and ex vivo permeation. The lead formulation exhibited desired physicochemical characteristics, an extended release of GTX over a 12 h period, and was stable over three months at the three storage conditions (refrigerated, room temperature, and accelerated). The transcorneal flux and permeability of GTX from the GTX-NLC formulation were 5.5- and 6.0-fold higher in comparison to the commercial eyedrops and exhibited a similar in vitro antibacterial activity. Therefore, GTX-NLCs could serve as an alternative drug delivery platform to improve treatment outcomes in BC.
摘要：
细菌性结膜炎（BC）引起眼粘膜的炎症。早期有效治疗BC可以防止感染扩散到眼内组织，这可能导致细菌性眼内炎或严重的视力障碍。2003年，加替沙星（GTX）滴眼液作为一种新的广谱氟喹诺酮类药物被引入治疗BC。随后，GTX的使用扩展到其他眼部细菌感染。然而,由于角膜前损失和不良的眼部生物利用度，商业眼药水的频繁管理是必要的，导致患者依从性差。因此，当前调查的目标是在基于脂质的药物递送系统中配制GTX，以克服现有市售滴眼液的挑战，因此，改善细菌性结膜炎的管理。GTX-NLC和SLN用热均质化-探针超声处理方法配制。对GTX-NLC先导制剂进行了表征和体外药物释放评估，抗菌效果（耐甲氧西林金黄色葡萄球菌和铜绿假单胞菌），和离体渗透。先导制剂表现出期望的物理化学特性，在12小时内延长释放GTX，在三种储存条件(冷藏，室温,并加速）。与商业滴眼液相比，来自GTX-NLC制剂的GTX的跨角膜通量和渗透性高5.5和6.0倍，并表现出相似的体外抗菌活性。因此,GTX-NLC可以作为替代药物递送平台来改善BC的治疗结果。
