2026-06-27T15:46:58Zhttps://docta.ucm.es/rest/oai/requestoai:docta.ucm.es:20.500.14352/62392023-08-28T08:55:13Zcom_20.500.14352_14col_20.500.14352_15
Docta Complutense
author
Yadav, Monika
author
Schiavone, Nicola
author
Guzmán Aránguez, Ana Isabel
author
Giansanti, Fabrizio
author
Papucci, Laura
author
Pérez de Lara, María Jesús
author
Singh, Mandeep
author
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
Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD)
journal article
URL
https://docta.ucm.es/bitstreams/529935fb-5041-4278-bc38-285287d0edd2/download
File
MD5
cbf04493fd2387c144e2c42057505d1a
1386087
application/pdf
Aranguez_Yadav2020_Article_Atorvastatin-loadedSolidLipidN.pdf