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Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD)

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Yadav, Monika and Schiavone, Nicola and Guzmán Aránguez, Ana Isabel and Giansanti, Fabrizio and Papucci, Laura and Pérez de Lara, María Jesús and Singh, Mandeep and Kaur, Indu Pal (2020) Atorvastatin-loaded solid lipid nanoparticles as eye drops: proposed treatment option for age-related macular degeneration (AMD). Drug Delivery and Translational Research . ISSN 2190-393X

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Official URL: https://doi.org/10.1007/s13346-020-00777-6




Abstract

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.


Item Type:Article
Uncontrolled Keywords:Ocular delivery, In vivo safety, Uptake studies, Ocular pharmacokinetics, Posterior eye delivery, Statins, Nanostructured carriers
Subjects:Sciences > Chemistry > Biochemistry
Medical sciences > Medicine > Ophtalmology
Medical sciences > Optics > Eyes anatomy
ID Code:60467
Deposited On:13 May 2020 08:12
Last Modified:13 May 2020 10:09

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