Appell Matthew B, Malmberg Kiersten, Pasupathy Ashwin, Josyula Aditya, Ortiz Jairo, McDonnell Peter J, Shekhawat Nakul, Parikh Kunal S, Ensign Laura M
The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Pharmacology and Molecular Sciences, Johns Hopkins University School of Medicine, Baltimore, MD 21231, USA.
The Center for Nanomedicine, The Wilmer Eye Institute, Johns Hopkins University School of Medicine, 400 N Broadway, Baltimore, MD 21231, USA; Department of Chemical and Biomolecular Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
J Control Release. 2025 May 10;381:113634. doi: 10.1016/j.jconrel.2025.113634. Epub 2025 Mar 15.
Ocular infections may arise spontaneously or following penetrating globe injury or operation, such as corneal transplant or cataract extraction. Treatment and prophylaxis of bacterial infections using antibiotic eye drops requires a strict dosing regimen to avoid irreversible vision loss. At present, moxifloxacin eye drops are prescribed for use multiple times per day, leading to patient non-adherence, the emergence of bacterial resistance, and infection progression. The desire to avoid sub-lethal antibiotic dosing and visual impairment through inconsistent eye drop application motivates the development of a sustained release injectable formulation. Herein, we report the development of an ion-paired, nanocrystalline moxifloxacin formulation that provided increased intraocular antibiotic accumulation with a single subconjunctival injection compared to 3× daily eye drops. The sustained release functionality further led to improved or non-inferior prevention and treatment of Staphylococcus aureus-induced ocular infection in both rats and rabbits compared to gold standard intracameral moxifloxacin and moxifloxacin eye drops. By achieving therapeutically relevant moxifloxacin accumulation, this nanocrystalline moxifloxacin formulation may be a promising alternative to conventional therapies to achieve improved post-surgical infection prevention and bacterial keratitis treatment outcomes.
眼部感染可能自发出现，也可能发生在眼球穿透性损伤或手术后，如角膜移植或白内障摘除术后。使用抗生素眼药水治疗和预防细菌感染需要严格的给药方案，以避免不可逆转的视力丧失。目前，莫西沙星眼药水需每天多次给药，这导致患者依从性差、细菌耐药性出现以及感染进展。通过不一致的眼药水应用来避免亚致死性抗生素给药和视力损害的需求推动了一种缓释注射制剂的研发。在此，我们报告了一种离子对纳米晶莫西沙星制剂的研发情况，与每日3次滴眼相比，单次结膜下注射该制剂可增加眼内抗生素蓄积。与金标准前房内注射莫西沙星和莫西沙星眼药水相比，该缓释功能还使大鼠和家兔的金黄色葡萄球菌诱导的眼部感染的预防和治疗得到改善或不劣于后者。通过实现与治疗相关的莫西沙星蓄积，这种纳米晶莫西沙星制剂可能是传统疗法的一种有前景的替代方案，以改善术后感染预防和细菌性角膜炎的治疗效果。
