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

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.

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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.

    Article  PubMed  Google Scholar 

  2. 2.

    Zarbin M, Szirth B. Current treatment of age-related macular degeneration. Optom Vis Sci. 2007;84:559–72.

    Article  PubMed  Google Scholar 

  3. 3.

    Kimura H, Yasukawa T, Tabata Y, Ogura Y. Drug targeting to choroidal neovascularization. Adv Drug Deliv Rev. 2001;52:79–91.

    CAS  Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    Article  Google 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.

    Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    Article  Google 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.

    CAS  Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    Article  PubMed  Google 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.

    CAS  Article  PubMed  Google 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.

    Article  Google Scholar 

  21. 21.

    Meek KM, Fullwood NJ. Corneal and scleral collagens—a microscopist’s perspective. Micron. 2001;32:261–72.

    CAS  Article  PubMed  Google 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.

    CAS  Article  Google 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.

    CAS  PubMed  Google 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.

    CAS  Article  PubMed  Google Scholar 

  25. 25.

    Peyman GA, Lad EM, Moshfeghi DM. Intravitreal injection of therapeutic agents. Retina. 2009;29:875–912.

    Article  PubMed  Google Scholar 

  26. 26.

    Mittl RN, Tiwari R. Suprachoroidal injection of sodium hyaluronate as an ‘internal’ buckling procedure. Ophthalmol Res. 1987;19:255–60.

    CAS  Article  Google Scholar 

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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.

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Correspondence to Henry F. Edelhauser or Mark R. Prausnitz.

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Patel, S.R., Lin, A.S.P., Edelhauser, H.F. et al. Suprachoroidal Drug Delivery to the Back of the Eye Using Hollow Microneedles. Pharm Res 28, 166–176 (2011). https://doi.org/10.1007/s11095-010-0271-y

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KEY WORDS

  • eye suprachoroidal space
  • hollow microneedle
  • microparticle
  • nanoparticle
  • ocular drug delivery