Safety study of intravitreal and suprachoroidal Laponite clay
in rabbit eyes
Alba De Martino
María J. Rodrigo
José M. Fraile
José A. Mayoral
Received: 29 March 2017 / Revised: 3 December 2017 /Accepted: 28 December 2017 / Published online: 20 January 2018
Springer-Verlag GmbH Germany, part of Springer Nature 2018
Purpose To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administra-
tion in rabbit eyes.
Methods Thirty-two New Zealand albino rabbits were divided into two experimental groups to test intravitreal (IVT group) and
suprachoroidal (SCS group) administration of a 100-μl and 50-μl Laponite suspension respectively. Following injection, the eyes
were monitored by ocular tonometry, slit-lamp eye examination and indirect ophthalmoscopy, at 24 h, 1, 4, 12, and 14 weeks post
administration. Histological examination was also performed to determine whether any ocular pathological change had occurred.
Throughout the study, LAP presence in vitreous was estimated by complexometric titration with ethylenediaminetetraacetic acid
(EDTA), taking advantage of the Laponite high content of magnesium ions.
Results Neither significant differences in the intraocular pressure, nor relevant ocular complications were found in the two
experimental groups after LAP administration. The histology of the retina remained unchanged. LAP presence in vitreous could
be indirectly confirmed by complexometric titration until 14 weeks post administration in eyes of IVT group.
Conclusion Laponite could be considered as a vehicle for potential clinical use in ocular drug administration, due to its proven
ocular biocompatibility and its transparency in gel state.
The development of new vehicles and drug formulations that
increase patient compliance and enhance the drug bioavail-
ability represents an important aspect in controlling the evo-
lution of different ocular diseases. In this sense, different
sustained-release drug delivery systems have been developed
to overcome eye drops limitations . These systems can
achieve prolonged therapeutic drug concentrations in ocular
target tissues, while limiting systemic exposure and side-ef-
fects, and improving patient adherence to therapy. As a result,
trans-scleral and intravitreal drug delivery systems have had
increasing importance in the treatment of retinal diseases .
Different systems containing clays and clay minerals
(natural clays, synthetic clays, clay–polymers composites,
films, and hydrogels) have been used in the pharmaceuti-
vectorize the release of drugs and consequently increasing
their bioavailability .
* Esther Prieto
Ophthalmology Department, Hospital Universitario Miguel Servet,
Paseo Isabel la Católica 1-3, E-50009 Zaragoza, Spain
Instituto de Investigación Sanitaria de Aragón (IIS-Aragón), Avda.
San Juan Bosco 13, E-50009 Zaragoza, Spain
Laboratorio de Cromatografía y Espectroscopia, Instituto de Síntesis
Química y Catálisis Homogénea (ISQCH), Facultad de Ciencias,
Universidad de Zaragoza-CSIC, C/ Pedro Cerbuna 12,
E-50009 Zaragoza, Spain
Histopathology Core Unit, Centro Nacional de Investigaciones
Oncológicas (CNIO), C/ Melchor Fernández Almagro 3,
E-28029 Madrid, Spain
Instituto de Síntesis Química y Catálisis Homogénea (ISQCH),
Facultad de Ciencias, Universidad de Zaragoza-CSIC, C/ Pedro
Cerbuna 12, E-50009 Zaragoza, Spain
Graefe's Archive for Clinical and Experimental Ophthalmology (2018) 256:535–546