Novel customized age-dependent corneal membranes and interactions with biodegradable nanoparticles loaded with dexibuprofen

Abstract

<span style="color:rgb( 31 , 31 , 31 )">Ocular inflammation is one of the most prevalent diseases in ophthalmology and it is currently treated using eye drops of </span>nonsteroidal antiinflammatory drugs<span style="color:rgb( 31 , 31 , 31 )"> such as </span>dexibuprofen<span style="color:rgb( 31 , 31 , 31 )"> (DXI). However, their bioavailability is low and therefore, PLGA </span>nanoparticles<span style="color:rgb( 31 , 31 , 31 )"> constitute a suitable approach to be administered as eyedrops. Therefore, DXI has been encapsulated into PLGA </span>nanoparticles<span style="color:rgb( 31 , 31 , 31 )"> (DXI-NPs). Although the eye, and specifically the cornea, suffers from age-related changes in its </span>composition<span style="color:rgb( 31 , 31 , 31 )">, current medications are not focused on these variations. Therefore, to elucidate the interaction mechanism of DXI-NPs with the cornea in relation with age, two different corneal </span>membrane models<span style="color:rgb( 31 , 31 , 31 )"> have been developed (corresponding to adult and </span>elder<span style="color:rgb( 31 , 31 , 31 )"> population) using </span>lipid monolayers<span style="color:rgb( 31 , 31 , 31 )">, large and giant </span>unilamellar vesicles<span style="color:rgb( 31 , 31 , 31 )">. Interactions of both DXI and DXI-NPs were studied with these models by means of Langmuir balance technique, dipole potential, anisotropy and </span>confocal microscopy<span style="color:rgb( 31 , 31 , 31 )">. In addition, fluorescently labelled </span>nanoparticles<span style="color:rgb( 31 , 31 , 31 )"> were administered to </span>mice<span style="color:rgb( 31 , 31 , 31 )"> in order to corroborate these data obtained </span><em style="color:rgb( 31 , 31 , 31 )">in vitro</em><span style="color:rgb( 31 , 31 , 31 )">. It was observed that DXI-NPs interact with </span>lipid membranes<span style="color:rgb( 31 , 31 , 31 )"> through an adhesion process, mainly in the rigid regions and afterwards DXI-NPs are internalized by a wrapping process. Furthermore, differences on the dipole potential caused by DXI-NPs in each corneal membrane have been obtained due to the increase of membrane </span>rigidity<span style="color:rgb( 31 , 31 , 31 )"> on the </span>ECMM<span style="color:rgb( 31 , 31 , 31 )">. Additionally, it can be confirmed that DXI-NPs adhere to Lo phase and also inside the lipid membrane. Finally, </span><em style="color:rgb( 31 , 31 , 31 )">in vitro</em><span style="color:rgb( 31 , 31 , 31 )"> and </span><em style="color:rgb( 31 , 31 , 31 )">in vivo</em><span style="color:rgb( 31 , 31 , 31 )"> results corroborate that DXI-NPs are adhered to the more ordered phase. Finally, differences between interactions of DXI-NPs with the elder and adult </span>corneal tissue<span style="color:rgb( 31 , 31 , 31 )"> were observed.</span>