2026-06-26T16:25:29Zhttps://docta.ucm.es/rest/oai/request

oai:docta.ucm.es:20.500.14352/62392023-08-28T08:55:13Zcom_20.500.14352_14col_20.500.14352_15

Yadav, Monika Schiavone, Nicola Guzmán Aránguez, Ana Isabel Giansanti, Fabrizio Papucci, Laura Pérez de Lara, María Jesús Singh, Mandeep Kaur, Indu Pal 2023-06-16T15:17:52Z 2023-06-16T15:17:52Z 2020-04-08 2190-393X 10.1007/s13346-020-00777-6 https://hdl.handle.net/20.500.14352/6239 https://doi.org/10.1007/s13346-020-00777-6 https://link.springer.com/article/10.1007%2Fs13346-020-00733-4#article-info Statins, 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. eng restricted access Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD) journal article