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Pharmaceutical Research

, Volume 28, Issue 1, pp 166–176 | Cite as

Suprachoroidal Drug Delivery to the Back of the Eye Using Hollow Microneedles

  • Samirkumar R. Patel
  • Angela S. P. Lin
  • Henry F. Edelhauser
  • Mark R. Prausnitz
Research Paper

ABSTRACT

Purpose

In this work, we tested the hypothesis that microneedles provide a minimally invasive method to inject particles into the suprachoroidal space for drug delivery to the back of the eye.

Methods

A single, hollow microneedle was inserted into the sclera, and infused nanoparticle and microparticle suspensions into the suprachoroidal space. Experiments were performed on whole rabbit, pig, and human eyes ex vivo. Particle delivery was imaged using brightfield and fluorescence microscopy as well as microcomputed tomography.

Results

Microneedles were shown to deliver sulforhodamine B as well as nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig, and human eyes. Volumes up to 35 μL were administered consistently. Optimization of the delivery device parameters showed that microneedle length, pressure, and particle size played an important role in determining successful delivery into the suprachoroidal space. Needle lengths of 800–1,000 μm and applied pressures of 250–300 kPa provided most reliable delivery.

Conclusions

Microneedles were shown for the first time to deliver nanoparticle and microparticle suspensions into the suprachoroidal space of rabbit, pig and human eyes. This shows that microneedles may provide a minimally invasive method for controlled drug delivery to the back of the eye.

KEY WORDS

eye suprachoroidal space hollow microneedle microparticle nanoparticle ocular drug delivery 

Notes

ACKNOWLEDGEMENTS

We would like to thank Dr. Harvinder Gill and Dr. John Nickerson for helpful discussions and Donna Bondy for administrative support. This work was carried out at the Emory Eye Center and at the Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience at Georgia Tech. This work was supported in part by the National Eye Institute (R24-EY-017045). M.R.P. serves as a consultant and is an inventor on patents licensed to companies developing microneedle-based products. This possible conflict of interest has been disclosed and is being managed by Georgia Tech and Emory University.

REFERENCES

  1. 1.
    del Amo EM, Urtti A. Current and future ophthalmic drug delivery systems: a shift to the posterior segment. Drug Discov Today. 2008;13:135–43.CrossRefPubMedGoogle Scholar
  2. 2.
    Zarbin M, Szirth B. Current treatment of age-related macular degeneration. Optom Vis Sci. 2007;84:559–72.CrossRefPubMedGoogle Scholar
  3. 3.
    Kimura H, Yasukawa T, Tabata Y, Ogura Y. Drug targeting to choroidal neovascularization. Adv Drug Deliv Rev. 2001;52:79–91.CrossRefPubMedGoogle Scholar
  4. 4.
    Ghate D, Brooks W, McCarey BE, Edelhauser HF. Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry. Invest Ophthalmol Vis Sci. 2007;48:2230–7.CrossRefPubMedGoogle Scholar
  5. 5.
    Kim SH, Lutz RJ, Wang NS, Robinson MR. Transport barriers in transscleral drug delivery for retinal diseases. Ophthalmic Res. 2007;39:244–54.CrossRefPubMedGoogle Scholar
  6. 6.
    Krohn J, Bertelsen T. Corrosion casts of the suprachoroidal space and uveoscleral drainage routes in the human eye. Acta Ophthalmol Scand. 1997;75:32–5.CrossRefPubMedGoogle Scholar
  7. 7.
    Krohn J, Bertelsen T. Light microscopy of uveoscleral drainage routes after gelatine injections into the suprachoroidal space. Acta Ophthalmol Scand. 1998;76:521–7.CrossRefPubMedGoogle Scholar
  8. 8.
    Einmahl S, Savoldelli M, D’Hermies F, Tabatabay C, Gurny R, Behar-Cohen F. Evaluation of a novel biomaterial in the suprachoroidal space of the rabbit eye. Invest Ophthalmol Vis Sci. 2002;43:1533–9.PubMedGoogle Scholar
  9. 9.
    Olsen TW, Feng X, Wabner K, Conston SR, Sierra DH, Folden DV, et al. Cannulation of the suprachoroidal space: a novel drug delivery methodology to the posterior segment. Am J Ophthalmol. 2006;142:777–87.CrossRefPubMedGoogle Scholar
  10. 10.
    Kim SH, Galban CJ, Lutz RJ, Dedrick RL, Csaky KG, Lizak MJ, et al. Assessment of subconjunctival and intrascleral drug delivery to the posterior segment using dynamic contrast-enhanced magnetic resonance imaging. Invest Ophthalmol Vis Sci. 2007;48:808–14.CrossRefPubMedGoogle Scholar
  11. 11.
    Gilger BC, Salmon JH, Wilkie DA, Cruysberg LP, Kim J, Hayat M, et al. A novel bioerodible deep scleral lamellar cyclosporine implant for uveitis. Invest Ophthalmol Vis Sci. 2006;47:2596–605.CrossRefPubMedGoogle Scholar
  12. 12.
    Gardeniers H, Luttge R, Berenschot EJW, de Boer MJ, Yeshurun SY, Hefetz M, et al. Silicon micromachined hollow microneedles for transdermal liquid transport. J Microelectromech Syst. 2003;12:855–62.CrossRefGoogle Scholar
  13. 13.
    Davis SP, Martanto W, Allen MG, Prausnitz MR. Hollow metal microneedles for insulin delivery to diabetic rats. IEEE Trans Biomed Eng. 2005;52:909–15.CrossRefPubMedGoogle Scholar
  14. 14.
    Brazzle J, Papautsky I, Frazier AB. Micromachined needle arrays for drug delivery or fluid extraction. IEEE Eng Med Biol Mag. 1999;18:53–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Zahn JD, Talbot NH, Liepmann D, Pisano AP. Microfabricated polysilicon microneedles for minimally invasive biomedical devices. Biomed Microdev. 2000;2:295–303.CrossRefGoogle Scholar
  16. 16.
    McAllister DV, Wang PM, Davis SP, Park JH, Canatella PJ, Allen MG, et al. Microfabricated needles for transdermal delivery of macromolecules and nanoparticles: fabrication methods and transport studies. Proc Natl Acad Sci USA. 2003;100:13755–60.CrossRefPubMedGoogle Scholar
  17. 17.
    Gupta J, Felner EI, Prausnitz MR. Minimally invasive insulin delivery in subjects with type 1 diabetes using hollow microneedles. Diabetes Technol Ther. 2009;11:329–37.CrossRefPubMedGoogle Scholar
  18. 18.
    Van Damme P, Oosterhuis-Kafeja F, Van der Wielen M, Almagor Y, Sharon O, Levin Y. Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults. Vaccine. 2009;27:454–9.CrossRefPubMedGoogle Scholar
  19. 19.
    Jiang J, Moore JS, Edelhauser HF, Prausnitz MR. Intrascleral drug delivery to the eye using hollow microneedles. Pharm Res. 2009;26:395–403.CrossRefPubMedGoogle Scholar
  20. 20.
    Feldkamp LA, Davis LC, Kress JW. Practical cone-beam algorithm. J Opt Soc Am A Opt Image Sci Vis. 1984;1:612–9.CrossRefGoogle Scholar
  21. 21.
    Meek KM, Fullwood NJ. Corneal and scleral collagens—a microscopist’s perspective. Micron. 2001;32:261–72.CrossRefPubMedGoogle Scholar
  22. 22.
    Edwards A, Prausnitz MR. Fiber matrix model of sclera and corneal stroma for drug delivery to the eye. AIChE J. 1998;44:214–25.CrossRefGoogle Scholar
  23. 23.
    Klein BEK, Klein R, Linton KLP. Intraocular pressure in an American community—the beaver damn eye study. Invest Ophthalmol Vis Sci. 1992;33:2224–8.PubMedGoogle Scholar
  24. 24.
    Martanto W, Moore JS, Kashlan O, Kamath R, Wang PM, O’Neal JM, et al. Microinfusion using hollow microneedles. Pharm Res. 2006;23:104–13.CrossRefPubMedGoogle Scholar
  25. 25.
    Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina. 2009;29:875–912.CrossRefPubMedGoogle Scholar
  26. 26.
    Mittl RN, Tiwari R. Suprachoroidal injection of sodium hyaluronate as an ‘internal’ buckling procedure. Ophthalmol Res. 1987;19:255–60.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.School of Chemical and Biomolecular EngineeringGeorgia Institute of TechnologyAtlantaUSA
  2. 2.Woodruff School of Mechanical EngineeringGeorgia Institute of TechnologyAtlantaUSA
  3. 3.Emory Eye CenterEmory UniversityAtlantaUSA

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