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Laponite clay as a carrier for intravitreal dexamethasone release

AuthorsFraile, José M. ; Garcia-Martin, Elena; Gil, Cristina; Mayoral, José A. ; Pablo, Luis E.; Polo-Llorens, Vicente; Prieto, Esther; Vispe, Eugenio
Issue Date2017
CitationXVI International Clay Conference (2017)
AbstractIntravitreal injection is considered an effective approach for treatment of posterior segment ocular diseases, as it delivers the therapeutic agent directly into the eye, but it presents some potential risks associated to the need for repeated injections. Alternative drug delivery systems are being developed to overcome this kind of limitations by reducing the frequency of injections, for example using biodegradable polymeric implants for slow release of dexamethasone (an anti-inflammatory steroid), but this methodology requires a surgical intervention to implant the material. Clays have been recently envisaged as carriers for drug delivery, but they had never been used for ophthalmic treatment. Laponite (LAP) is a white synthetic smectite clay, able to form transparent colloidal dispersions in water. We have demonstrated that dexamethasone (DEX), in spite of being a neutral molecule, is retained on laponite through weak interactions, mainly hydrogen bonds, as shown by solid state NMR. In vitro studies have shown that dexamethasone is released below its solubility in saline solution or in a model of vitreous humor, under equilibrium conditions. The in vivo ocular biocompatibility of laponite has been assessed by eye examination (slit lamp and indirect ophthalmoscopy) after intravitreal administration to rabbits. The clay did not elicit any inflammatory response even if the clay could be observed floating into the vitreous body as a transparent gel from day 1 through week 14 postadministration. The small amount of eyes with cataract were probably due to a traumatic effect associated with the injection technique because the histological examination did not show any change in eye's lens structure. Thus, laponite could be considered as a vehicle for potential clinical use in ocular drug administration due to its proved ocular biocompatibility and its transparency in the gel state. Moreover, Mg content in vitreous humor showed a decrease along the 14 weeks. About 33% of total initial LAP-dose administered could be detected in vitreous humor for up to 14 weeks postadministration, indicating some kind of degradation and/or elimination of the clay through an unknown mechanism. Intravitreal injections of 100 μL dexamethasone/laponite dispersion (10 mg solid/mL, 1:10 DEX/LAP w/w) were performed in albino rabbits (New Zealand) and DEX concentrations in vitreous humor were monitored over 24 weeks. Vitreous dexamethasone levels remained relatively stable from 7th day postadministration, and showed an elimination rate significantly lower than that found after intravitreal injection of dexamethasone in solution (1 mg/mL) (CL= 0.49 vs 315.29 g/day). The administration of DEX loading to laponite can lengthen the half-life of the drug (T½-el= 132.75 vs 0.13 days) and enhance its clinical uses.
DescriptionResumen del trabajo presentado a la XVI International Clay Conference (ICC), celebrada en Granada (España) del 17 al 21 de julio de 2017.
Appears in Collections:(ISQCH) Comunicaciones congresos
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