Laponite for biomedical applications: An ophthalmological perspective

Abstract

Clay minerals have been applied in biomedicine for thousands of years. Laponite is a nanostructured synthetic clay with the capacity to retain and progressively release drugs. In recent years there has been a resurgence of interest in Laponite application in various biomedical areas. This is the first paper to review the potential biomedical applications of Laponite in ophthalmology. The introduction briefly covers the physical, chemical, rheological, and biocompatibility features of different routes of administration. After that, emphasis is placed on 1) drug delivery for antibiotics, anti-inflammatories, growth factors, other proteins, and cancer treatment; 2) bleeding prevention or treatment; and 3) tissue engineering through regenerative medicine using scaffolds in intraocular and extraocular tissue. Although most scientific research is not performed on the eye, both the findings and the new treatments resulting from that research are potentially applicable in ophthalmology since many of the drugs used are the same, the tissue evaluated in vitro or in vivo is also present in the eye, and the pathologies treated also occur in the eye. Finally, future prospects for this emerging field are discussed.

Graphical abstract

Fig. 1

Laponite properties for ophthalmological applications. Created in BioRender.com.

Fig. 2

Studies of Laponite conducted in the eye. Abbreviations: IOP: intraocular pressure; OCT: optical coherence tomography; ERG: electroretinography; w: weeks. Created in BioRender.com. A: Complexometric determination of Mg2+ in rabbit vitreous humor. Left: Eye not injected with Laponite dispersion: the blue color after addition of EBT indicates the absence of magnesium. Middle: Eye injected with Laponite dispersion: the pink color after addition of EBT indicates the presence of magnesium. Right: Color change in vitreous sample after titration with the required volume of EDTA. B: Laponite levels over time in the vitreous humor of intravitreous administered eyes. C: Representative photomicrographs showing histological sections of the retina from treated (left panel) and control eyes (right panel) at 14 weeks after injection (HE; magnification Å∼ 650). Top: Suprachoroidal administration. Bottom: Intravitreal injection. All retinal layers are preserved and no differences between treated and control eyes were observed in the 20-step sections assessed. The ganglion cell layer is facing the upper side of the photograph. In suprachoroidally administered eyes, virtual spaces can be seen at the junction line between the choroid and sclera (arrows). R: retina; Ch: choroid; and S: sclera. A, B and C: Data from Ref. [40] (CC BY 4.0 license). D: Dexamethasone concentrations in the vitreous humor after intravitreal and suprachoroidal administration of Laponite–Dexamethasone (1:10 w w−1) suspension (10 mg mL−1). E: Dexamethasone concentrations in the vitreous humor after intravitreal administration of Laponite–Dexamethasone suspension. F: Dexamethasone concentrations in the vitreous humor after intravitreal administration of Dexamethasone solution. D, E and F: Data from Ref. [48] (CC BY 4.0 license). G: Intraocular pressure curves. Eye comparison between the [non-BRI] cohort (rats with ocular hypertension) and the [Bri-Lap] cohort (rats with ocular hypertension and treated with an intravitreal injection of Laponite–Brimonidine formulation). H: PhNR amplitude (a and PhNR waves) was statistically significantly higher in eyes treated with the Bri-Lap formulation in comparison with hypertensive and untreated eyes in the [non-Bri] cohort. Abbreviations: RE: right eye; a wave: signal from photoreceptors; b wave: signal from intermediate cells; PhNR wave: signal from retinal ganglion cells. w: week; μV: microvolts; *p < 0.05: statistical differences. I: Retinal ganglion cell analysis in glaucomatous eyes. Top: Retinal ganglion cells were counted in radial sections of the eye along 2 mm of a linear region of the retina, corresponding to four areas, two on each side of the optic nerve head. Middle: Two representative images of the ganglion cell layer marked with anti-Brn3a corresponding to a treated (RE) and non-treated eye (LE) of the same animal. Arrows mark the positive nuclei. Bottom: The mean number of retinal ganglion cells per linear mm of retina was significantly higher in hypertensive eyes injected with Laponite–Brimonidine formulation than in the untreated eyes (RE 23.00 ± 0.39 vs. LE 20.66 ± 0.98, p = 0.040). Abbreviations: RE: right eye; LE: left eye; ILM: internal limiting membrane. Scale bars: top: 22.72 μm; middle: 5.8 μm. G, H and I: Data from Ref. [49] (CC BY 4.0 license). J: 3D reconstruction of the changes in the aggregates at 2 weeks and 8 weeks of follow-up. The reconstruction is shown from two different perspectives at each point in time. Abbreviations: N: nasal; I: inferior; S: superior; IF: intravitreal formulation. K: Positive linear correlation between drug levels and total aggregate area. OCT data in red; brimonidine data in blue; ■: 1 week;: 4 weeks; ●: 8 weeks; ▲: 24 weeks. J and K: Data from Ref. [28] (CC BY 4.0 license).

Fig. 3

Studies of Laponite not conducted in the eye, potentially applicable in ophthalmology. Abbreviations: ILGF-1: insulin-like growth factor-1; FGF: fibroblast growth factor; VEGF: vascular endothelial growth factor; BBB: blood–brain barrier; BRB: blood–retina barrier; 5-FU: 5-fluorouracil; ICG: indocyanine green; Si(OH)4: Orthosilicic acid; Li: Lithium ions; Mg: Magnesium ions. Created in BioRender.com.