Lipo-PEG nano-ocular formulation successfully encapsulates hydrophilic fluconazole and traverses corneal and non-corneal path to reach posterior eye segment

作者：Shilpa Kakkar, Mandeep Singh, Sankunny Mohan Karuppayil, Jayant S. Raut, Fabrizio Giansanti, Laura Papucci, Nicola Schiavone, Tapas Chandra Nag, Nan Gao, Fu‐Shin X. Yu, Mohhammad Ramzan, Indu Pal Kaur · 发表于：Journal of drug targeting · 年份：2021 · DOI：10.1080/1061186x.2020.1871483 · 被引用次数：25 · 研究领域：Advanced Drug Delivery Systems、Ocular Surface and Contact Lens、Advancements in Transdermal Drug Delivery

The present study describes a special lipid-polyethylene glycol matrix solid lipid nanoparticles (SLNs; 138 nm; −2.07 mV) for ocular delivery. Success of this matrix to encapsulate (entrapment efficiency − 62.09%) a hydrophilic drug, fluconazole (FCZ-SLNs), with no burst release (67% release in 24 h) usually observed with most water-soluble drugs, is described presently. The system showed 164.64% higher flux than the marketed drops (Zocon®) through porcine cornea. Encapsulation within SLNs and slow release did not compromise efficacy of FCZ-SLNs. Latter showed in vitro and in vivo antifungal effects, including antibiofilm effects comparable to free FCZ solution. Developed system was safe and stable (even to sterilisation by autoclaving); and showed optimal viscosity, refractive index and osmotic pressure. These SLNs could reach up to retina following application as drops. The mechanism of transport via corneal and non-corneal transcellular pathways is described by fluorescent and TEM images of mice eye cross sections. Particles streamed through the vitreous, crossed inner limiting membrane and reached the outer retinal layers.