Center of Pharmacology and Drug Research & Development, University Pharmacy Department of Pharmacy Administration, Semmelweis University, Hőgyes Endre Street 7-9, H-1092 Budapest, Hungary.
Department of Anatomy, Histology and Embryology Semmelweis University, Tűzoltó Street 58, H-1094 Budapest, Hungary.
Int J Mol Sci. 2024 Aug 25;25(17):9228. doi: 10.3390/ijms25179228.
A novel ophthalmic delivery system utilizing levofloxacin-loaded, preservative-free, nanofiber-based inserts was investigated. Polyvinyl alcohol (PVA) and Poloxamer 407 (Polox)were employed as matrix materials, while hydroxypropyl-beta-cyclodextrin (HP-β-CD) was a solubilizer. The formulations were prepared via electrospinning and characterized for fiber morphology, drug dissolution, cytotoxicity, and antimicrobial activity. Scanning electron microscopy confirmed uniform fibrous structures. Fourier Transform Infrared spectroscopy and X-ray diffraction analyses demonstrated the amorphous state of levofloxacin within the fibers. In vitro dissolution studies revealed a rapid (within 2 min) and complete drug release, with higher HP-β-CD levels slightly delaying the release. Cytotoxicity tests showed increased HP-β-CD concentrations induced irritation, that was mitigated by sodium hyaluronate. The antimicrobial efficacy of the nanofibers was comparable to conventional eye drops, with lower minimum inhibitory concentrations for most tested strains. The nanofibrous formulation prepared from a PVA-Polox-based viscous solution of the drug:CD 1:1 mol ratio, containing 0.4% (/) sodium hyaluronate) was identified as a particularly promising alternative formulation due to its rapid and complete dissolution, good biocompatibility, and effective antimicrobial properties. Its gelling properties indicate that the residence time on the eye surface can be increased, potentially reducing discomfort and enhancing therapeutic outcomes. The nanofibrous formulations enhanced antimicrobial efficacy, providing a preservative-free alternative that minimizes the potential eye irritation that might occur because of the preservative agent and reduces the administrated dose frequency by extending the drug's retention time on the eye's surface. Subsequently, it improves patients' adherence, which would reflect positively on the bioavailability. The levofloxacin-HP-β-CD nanofibers demonstrate promise as an alternative to traditional eye drops, offering advantages in solubility, stability, and patient compliance for ocular infection treatment.
利用左氧氟沙星负载、无防腐剂、基于纳米纤维的植入物开发了一种新型眼科给药系统。聚乙烯醇 (PVA) 和泊洛沙姆 407 (Polox) 用作基质材料，而羟丙基-β-环糊精 (HP-β-CD) 用作增溶剂。通过静电纺丝制备了这些配方，并对纤维形态、药物溶解、细胞毒性和抗菌活性进行了表征。扫描电子显微镜证实了纤维的均匀纤维结构。傅里叶变换红外光谱和 X 射线衍射分析表明，左氧氟沙星在纤维内处于无定形状态。体外溶解研究表明，药物迅速（在 2 分钟内）完全释放，较高的 HP-β-CD 水平略微延迟了释放。细胞毒性试验表明，较高的 HP-β-CD 浓度会引起刺激，而透明质酸钠可以减轻刺激。纳米纤维的抗菌效果与常规眼药水相当，对大多数测试菌株的最低抑菌浓度较低。由于其快速和完全溶解、良好的生物相容性和有效的抗菌性能，从 PVA-Polox 药物粘性溶液中制备的以药物：CD 1:1 摩尔比为基础、含有 0.4%（/）透明质酸钠的纳米纤维制剂被确定为一种特别有前途的替代制剂。由于其胶凝特性，可以增加在眼表面的停留时间，从而潜在地减少不适感并增强治疗效果。纳米纤维制剂增强了抗菌功效，提供了一种无防腐剂的替代方案，可以最大程度地减少防腐剂可能引起的眼部刺激，并通过延长药物在眼表面的滞留时间来减少给药频率。随后，它提高了患者的依从性，这将对生物利用度产生积极影响。左氧氟沙星-HP-β-CD 纳米纤维有望替代传统眼药水，在溶解性、稳定性和患者依从性方面为眼部感染治疗提供优势。
