Skip to main content

Advertisement

SpringerLink
Log in

Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes

  • Basic Science
  • Published:
Graefe's Archive for Clinical and Experimental Ophthalmology Aims and scope Submit manuscript

Abstract

Purpose

To study the safety and biocompatibility of Laponite clay (LAP) within an intravitreal and suprachoroidal administration 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Aggarwal D, Kaur IP (2005) Improved pharmacodynamics of timolol maleate from a mucoadhesive niosomal ophthalmic drug delivery system. Int J Pharm 290:155–159

    Article  CAS  PubMed  Google Scholar 

  2. Lee SS, Robinson MR (2009) Novel drug delivery systems for retinal diseases. A review. Ophthalmic Res 41:124–135

    Article  CAS  PubMed  Google Scholar 

  3. Rodrigues LA, Figueiras A, Veiga F, de Freitas RM, Nunes LC, da Silva Filho EC, da Silva Leite CM (2013) The systems containing clays and clay minerals from modified drug release: a review. Colloids Surf B Biointerfaces 103:642–651

    Article  CAS  PubMed  Google Scholar 

  4. Da Silva GR, Ayres E, Orefice RL, Moura SA, Cara DC, Cunha Ada S Jr (2009) Controlled release of dexamethasone acetate from biodegradable and biocompatible polyurethane and polyurethane nanocomposite. J Drug Target 17:374–383

    Article  PubMed  Google Scholar 

  5. Ruzicka B, Zulian L, Ruocco G (2006) More on the phase diagram of Laponite. Langmuir 22:1106–1111

    Article  CAS  PubMed  Google Scholar 

  6. Ghadiri M, Chrzanowski W, Rohanizadeh R (2014) Antibiotic eluting clay mineral (Laponite(R)) for wound healing application: an in vitro study. J Mater Sci Mater Med 25:2513–2526

    Article  CAS  PubMed  Google Scholar 

  7. Viseras C, Aguzzi C, Cerezo P, López-Galindo A (2007) Uses of clay minerals in semisolid health care and therapeutic products. Appl Clay Sci 36:37–50

    Article  CAS  Google Scholar 

  8. Wang C, Wang S, Li K, Ju Y, Li J, Zhang Y, Li J, Liu X, Shi X, Zhao Q (2014) Preparation of laponite bioceramics for potential bone tissue engineering applications. PLoS One 9:e99585

    Article  PubMed  PubMed Central  Google Scholar 

  9. European Directorate for the Quality of Medicines (EDQM) (2005) European pharmacopoeia, 5th edn. Council of Europe, Strasbourg, p 1958

    Google Scholar 

  10. Vogel AI (1989) Vogel’s textbook of quantitative chemical analysis, 5th edn. John Wiley and Sons, New York, pp 328–331

    Google Scholar 

  11. Fraile JM, Garcia-Martin E, Gil C, Mayoral JA, Pablo LE, Polo V, Prieto E, Vispe E (2016) Laponite as carrier for controlled in vitro delivery of dexamethasone in vitreous humor models. Eur J Pharm Biopharm 108:83–90

    Article  CAS  PubMed  Google Scholar 

  12. Harris DC (2007) Quantitative chemical analysis, 7th edn. WH Freeman and Company, New York, p 245

    Google Scholar 

  13. Achouri D, Alhanout K, Piccerelle P, Andrieu V (2013) Recent advances in ocular drug delivery. Drug Dev Ind Pharm 39:1599–1617

    Article  CAS  PubMed  Google Scholar 

  14. Kompella UB, Amrite AC, Pacha RR, Durazo SA (2013) Nanomedicines for back of the eye drug delivery, gene delivery, and imaging. Prog Retin Eye Res 36:172–198

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Chen M, Li X, Liu J, Han Y, Cheng L (2015) Safety and pharmacodynamics of suprachoroidal injection of triamcinolone acetonide as a controlled ocular drug release model. J Control Release 203:109–117

    Article  CAS  PubMed  Google Scholar 

  16. Han HK, Lee YC, Lee MY, Patil AJ, Shin HJ (2011) Magnesium and calcium organophyllosilicates: synthesis and in vitro cytotoxicity study. ACS Appl Mater Interfaces 3:2564–2572

    Article  CAS  PubMed  Google Scholar 

  17. Goncalves M, Figueira P, Maciel D, Rodrigues J, Shi X, Tomas H, Li Y (2014) Antitumor efficacy of doxorubicin-loaded laponite/alginate hybrid hydrogels. Macromol Biosci 14:110–120

    Article  CAS  PubMed  Google Scholar 

  18. Olsen TW, Feng X, Wabner K, Conston SR, Sierra DH, Folden DV, Smith ME, Cameron JD (2006) Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment. Am J Ophthalmol 142:777–787

    Article  CAS  PubMed  Google Scholar 

  19. Peng Y, Ang M, Foo S, Lee WS, Ma Z, Venkatraman SS, Wong TT (2011) Biocompatibility and biodegradation studies of subconjunctival implants in rabbit eyes. PLoS One 6:e22507

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Peng YJ, Kau YC, Wen CW, Liu KS, Liu SJ (2010) Solvent-free biodegradable scleral plugs providing sustained release of vancomycin, amikacin, and dexamethasone—an in vivo study. J Biomed Mater Res A 94:426–432

    PubMed  Google Scholar 

  21. Lambuk L, Jafri AJ, Arfuzir NN, Iezhitsa I, Agarwal R, Rozali KN, Agarwal P, Bakar NS, Kutty MK, Yusof AP, Krasilnikova A, Spasov A, Ozerov A, Ismail NM (2017) Neuroprotective effect of magnesium acetyltaurate against NMDA-induced excitotoxicity in rat retina. Neurotox Res 31:31–45

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Authors would like to acknowledge the collaboration of the staff members of the Centro de Investigación Biomédica de Aragón (CIBA) in animal supply, care, feeding, and maintenance services.

Author information

Authors and Affiliations

  1. Ophthalmology Department, Hospital Universitario Miguel Servet, Paseo Isabel la Católica 1-3, E-50009, Zaragoza, Spain

    Esther Prieto, Miriam Idoipe, María J. Rodrigo, Elena Garcia-Martin & Vicente Polo-Llorens

  2. Instituto de Investigación Sanitaria de Aragón (IIS-Aragón), Avda. San Juan Bosco 13, E-50009, Zaragoza, Spain

    Esther Prieto, Miriam Idoipe, María J. Rodrigo, Elena Garcia-Martin & Vicente Polo-Llorens

  3. 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

    Eugenio Vispe

  4. Histopathology Core Unit, Centro Nacional de Investigaciones Oncológicas (CNIO), C/ Melchor Fernández Almagro 3, E-28029, Madrid, Spain

    Alba De Martino

  5. Instituto de Síntesis Química y Catálisis Homogénea (ISQCH), Facultad de Ciencias, Universidad de Zaragoza-CSIC, C/ Pedro Cerbuna 12, E-50009, Zaragoza, Spain

    José M. Fraile & José A. Mayoral

Authors
  1. Esther Prieto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Eugenio Vispe
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Alba De Martino
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Miriam Idoipe
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. María J. Rodrigo
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Elena Garcia-Martin
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. José M. Fraile
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Vicente Polo-Llorens
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. José A. Mayoral
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Esther Prieto.

Ethics declarations

Author disclosure statement

All the listed authors agree with the submission of this manuscript, and none of them has any conflicting financial interests related to the submission, either currently or over the past 5 years.

Disclosure conflict of interest

This study has received financial support from the following institutions: Instituto de Salud Carlos III (grant PI12/02285), and Diputación General de Aragón (E11 Group co-financed by the European Regional Development Funds). The authors declare that they have no conflict of interest.

Ethical approval

All procedures performed in this study involving animals were in accordance with the ethical standards of the in-house Ethics Committee for Animal Experiments of the University of Zaragoza (Spain) at which the studies were conducted.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Prieto, E., Vispe, E., De Martino, A. et al. Safety study of intravitreal and suprachoroidal Laponite clay in rabbit eyes. Graefes Arch Clin Exp Ophthalmol 256, 535–546 (2018). https://doi.org/10.1007/s00417-017-3893-5

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00417-017-3893-5

Keywords

Search

Navigation