Yadav, MonikaSchiavone, NicolaGuzmán Aránguez, Ana IsabelGiansanti, FabrizioPapucci, LauraPérez de Lara, María JesúsSingh, MandeepKaur, Indu Pal2023-06-162023-06-162020-04-082190-393X10.1007/s13346-020-00777-6https://hdl.handle.net/20.500.14352/6239Statins, widely prescribed for cardiovascular diseases, are also being eyed for management of age-related macular degeneration (AMD). Poor bioavailability and blood-aqueous barrier may however limit significant ocular concentration of statins following oral administration. We for the first time propose and investigate local application of atorvastatin (ATS; representative statin) loaded into solid lipid nanoparticles (SLNs), as self-administrable eye drops. Insolubility, instability, and high molecular weight > 500 of ATS, and ensuring that SLNs reach posterior eye were the challenges to be met. ATS-SLNs, developed (2339/DEL/2014) using suitable components, quality-by-design (QBD) approach, and scalable hot high-pressure homogenization, were characterized and evaluated comprehensively for ocular suitability. ATS-SLNs were 8 and 12 times more bioavailable (AUC) in aqueous and vitreous humor, respectively, than free ATS. Three-tier (in vitro, ex vivo, and in vivo) ocular safety, higher corneal flux (2.5-fold), and improved stability (13.62 times) including photostability of ATS on incorporation in ATS-SLNs were established. Autoclavability and aqueous nature are the other highlights of ATS-SLNs. Presence of intact fluorescein-labeled SLNs (F-SLNs) in internal eye tissues post–in vivo application as eye drops provides direct evidence of successful delivery. Perinuclear fluorescence in ARPE-19 cells confirms the effective uptake of F-SLNs. Prolonged residence, up to 7 h, was attributed to the mucus-penetrating nature of ATS-SLNs.engjournal articlehttps://doi.org/10.1007/s13346-020-00777-6https://link.springer.com/article/10.1007%2Fs13346-020-00733-4#article-inforestricted access617.736615.216.84615.015Ocular deliveryIn vivo safetyUptake studiesOcular pharmacokineticsPosterior eye deliveryStatinsNanostructured carriersBioquímica (Química)OftalmologíaAnatomía ocular3201.09 Oftalmología