Noble Metals and Soft Bio-Inspired Nanoparticles in Retinal Diseases Treatment: A Perspective

Abstract

We are witnessing an exponential increase in the use of different nanomaterials in a plethora of biomedical fields. We are all aware of how nanoparticles (NPs) have influenced and revolutionized the way we supply drugs or how to use them as therapeutic agents thanks to their tunable physico-chemical properties. However, there is still a niche of applications where NP have not yet been widely explored. This is the field of ocular delivery and NP-based therapy, which characterizes the topic of the current review. In particular, many efforts are being made to develop nanosystems capable of reaching deeper sections of the eye such as the retina. Particular attention will be given here to noble metal (gold and silver), and to polymeric nanoparticles, systems consisting of lipid bilayers such as liposomes or vesicles based on nonionic surfactant. We will report here the most relevant literature on the use of different types of NPs for an efficient delivery of drugs and bio-macromolecules to the eyes or as active therapeutic tools.

Keywords: bio-inspired NPs; drug delivery; noble metals NPs; retinal diseases.

Figure 1

Retinal neuronal and vascular structure and retinal disease. (A) Diagram of a human eye. Light passes through the pupil and is focused by lens onto macula of the retinal layer at the back of the eye. (B) Retina consists of three layers of neurons, photoreceptor, bipolar, and ganglion cells. The retinal pigment epithelial (RPE) monolayer together with Bruch’s membrane (BM) form outer blood retinal barrier that separates the neuroretina from the choroid. Choroidal circulation provides oxygen and nutrients to outer retina. (C) The retina has an interconnected network of three vascular layers located in the ganglion cell/nerve fiber layer, inner plexiform layer (IPL), and outer plexiform layer (OPL). (D) retinal tissue and cells that are affected under different disease conditions. Adapted from reference [17].

Figure 2

Common drug administration routes through the eye. Topical administration (1,2), subconjunctival injection (periocular route) (3), subretinal injection (4), and intravitreal injection (5). Adapted from reference [31].

Figure 3

Schematic representation of gold nanodisks (GNDs) effects in retinal degeneration and Optical Coherence Tomography (OCT) imaging. The GNDs were particularly suitable for their optical properties connected to the shape: GNDs absorbed in the Near Infrared Region (NIR). The size and surface charge also influenced the eye diffusion. In OCT images, GNDs exhibited a strong signal compared to the dual window (DW) processing method, which is used to detect modulation of OCT signals due to scattering or absorption. Reprinted from [80] Copyright (2017), with permission from Elsevier.

Figure 4

(A) Protection evaluation against photo-oxidative retinal damage in a light-damaged animal model by the use of different formulation: chrysophanol–berberine hydrochloride suspension (CBs), compound liposomes (CBLs), and PAMAM coated compound liposomes (P-CBLs). Retina was stained with hematoxilyn/eosin (scale bare = 20 µm). (B) Fundus retinography after incubation with the different formulations. Adapted from [99] under the terms of the Creative Commons Attribution 4.0 International License.

Figure 5

Fluorescence immonostaining by GFP expression in embrionary rat retinal primary cells. The green signal was referred to the transfection event of DST20 nioplexes with MC-GFP, (B) pGFP 3.5 kb, or (C) pEGFP 5.5 kb. (D–F) Positive controls incubated with Lipofectamine™ 2000. Nuclei were stained with Hoechst 33,342 (blue) and neuronal dendrites with MAP2 (red). Scale bars: 20 μm. Reprinted from [116] Copyright (2019), with permission from Elsevier.

Figure 6

Fundus camera acquisitions of rabbits’ eyes after hybrid polyamidoamine (PAMAM) dendrimer hydrogel/poly(lacticco-glycolic acid) (PLGA) nanoparticle platform (HDNP) and NP Formulations (NP) topical administration FluoSpheres were confined in nanosistems to follow the distribution and retention in the eye. The analysis was performed at the end of 1, 3, 5, and 7 days of formulations instillation. Left: regular fundus camera images of the eyes; right: fluorescent fundus camera images. Adapted with permission from [150], copyright (2012), American Chemical Society.

Figure 7

(a) SEM and ESB-SEM images of the micropropellers. (b,c) incomplete rotation of an uncoated micropropeller for one period (p) in the vitreous was showed in schematic and time-lapse microscopy, whereas the coated propeller exhibited propulsion under magnetic stimuli in vitreous for 1.5 s (nine periods). Red arrows showed the propulsion direction of propeller. The original position of nanotools and after the rotating magnetic field application were showed with green and red dashed lines. Scale bars, 1 µm. (d) Schematic illustration of micropropeller movement in the vitreous. (e) Left: fluorescent acquisitions showed the micropropellers labelled red on retina. Right: passive fluorescent particles were accumulated near center of vitreous. Nuclei of cells were stained with DAPI. Scale bar, 20 µm. Adapted from reference [155] under the terms of the Creative Commons Attribution-Non Commercial license.