Skip to main content

Advertisement

SpringerLink
Log in

Intrascleral Drug Delivery to the Eye Using Hollow Microneedles

  • Research Paper
  • Published:
Pharmaceutical Research Aims and scope Submit manuscript

Abstract

Purpose

This study tested the hypothesis that hollow microneedles can infuse solutions containing soluble molecules, nanoparticles, and microparticles into sclera in a minimally invasive manner.

Methods

Individual hollow microneedles were inserted into, but not across, human cadaver sclera and aqueous solutions containing sulforhodamine or fluorescently tagged nanoparticles or microparticles were infused into sclera at constant pressure. The infused volume of fluid was measured and imaged histologically as a function of scleral thickness, infusion pressure, needle retraction depth and the presence of spreading enzymes (hyaluronidase and collagenase).

Results

Individual hollow microneedles were able to insert into sclera. Fluid infusion was extremely slow after microneedle insertion into the sclera without retraction, but partial retraction of the microneedle over a distance of 200–300 μm enabled infusion of 10–35 μl of fluid into the tissue. Scleral thickness and infusion pressure had insignificant effects on fluid delivery. Nanoparticle suspensions were also delivered into sclera, but microparticles were delivered only in the presence of hyaluronidase and collagenase spreading enzymes, which suggested the role of scleral glycosaminoglycans and collagen fibers as rate-limiting barriers.

Conclusion

This study shows that hollow microneedles can infuse solutions into the sclera for minimally invasive delivery of soluble molecules, nanoparticles and microparticles.

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. D. Ghate, and H. F. Edelhauser. Ocular drug delivery. Expert Opin. Drug Deliv. 3:275–287 (2006).

    Article  PubMed  CAS  Google Scholar 

  2. E. M. Del Amo, and A. Urtti. Current and future ophthalmic drug delivery systems. A shift to the posterior segment. Drug Discov. Today. 13:135–143 (2008).

    Article  PubMed  CAS  Google Scholar 

  3. D. M. Maurice. Drug delivery to the posterior segment from drops. Surv. Ophthalmol. 47(Suppl 1):S41–52 (2002).

    Article  PubMed  Google Scholar 

  4. R. D. Jager, L. P. Aiello, S. C. Patel, and E. T. Cunningham Jr. Risks of intravitreous injection: a comprehensive review. Retina. 24:676–698 (2004).

    Article  PubMed  Google Scholar 

  5. D. H. Geroski, and H. F. Edelhauser. Transscleral drug delivery for posterior segment disease. Adv. Drug Deliv. Rev. 52:37–48 (2001).

    Article  PubMed  CAS  Google Scholar 

  6. S. H. Kim, R. J. Lutz, N. S. Wang, and M. R. Robinson. Transport barriers in transscleral drug delivery for retinal diseases. Ophthalmic. Res. 39:244–254 (2007).

    Article  PubMed  CAS  Google Scholar 

  7. I. Fatt, and B. A. Weissman. Physiology of the Eye: An Introduction to the Vegetative Functions. Butterworth-Heinemann, Boston, 1992.

    Google Scholar 

  8. O. Weijtens, E. J. Feron, R. C. Schoemaker, A. F. Cohen, G. W. M. Lentjes, F. P. H. T. M. Romijn, and J. C. v. Meurs. High concentrations of dexamethasone in aqueous and vitreous after subconjunctival injection. Am. J. Ophthamal. 1999:192–197 (1999)August.

    Article  Google Scholar 

  9. T. W. Lee, and J. R. Robinson. Drug delivery to the posterior segment of the eye: some insights on the penetration pathways after subconjunctival injection. J. Ocular Pharmacol. Ther. 17:565–572 (2001).

    Article  CAS  Google Scholar 

  10. S. B. Lee, D. H. Geroski, M. R. Prausnitz, and H. F. Edelhauser. Drug delivery through the sclera: effects of thickness, hydration, and sustained release systems. Exp. Eye Res. 78:599–607 (2004).

    Article  PubMed  CAS  Google Scholar 

  11. T. Yasukawa, Y. Ogura, H. Kimura, E. Sakurai, and Y. Tabata. Drug delivery from ocular implants. Expert Opin. Drug Deliv. 3:261–273 (2006).

    Article  PubMed  CAS  Google Scholar 

  12. E. Eljarrat-Binstock, and A. J. Domb. Iontophoresis: a non-invasive ocular drug delivery. J. Control Release. 110:479–489 (2006).

    Article  PubMed  CAS  Google Scholar 

  13. M. R. Prausnitz, H. S. Gill, and J.-H. Park. Microneedles for drug delivery. In M. J. Rathbone, J. Hadgraft, M. S. Roberts, and M. E. Lane (eds.), Modified Release Drug Delivery, Informa Healthcare, New York, 2008.

    Google Scholar 

  14. M. R. Prausnitz, J. A. Mikszta, M. Cormier, and A. K. Andrianov. Microneedle-based vaccines. Curr. Top Microbiol. Immunol. (2008, in press).

  15. M. L. Reed, and W.-K. Lye. Microsystems for drug and gene delivery. Proc. IEEE. 92:56–75 (2004).

    Article  CAS  Google Scholar 

  16. W. Martanto, J. S. Moore, T. Couse, and M. R. Prausnitz. Mechanism of fluid infusion during microneedle insertion and retraction. J. Control Release. 112:357–361 (2006).

    Article  PubMed  CAS  Google Scholar 

  17. W. Martanto, J. S. Moore, O. Kashlan, R. Kamath, P. M. Wang, J. M. O’Neal, and M. R. Prausnitz. Microinfusion using hollow microneedles. Pharm. Res. 23:104–113 (2006).

    Article  PubMed  CAS  Google Scholar 

  18. H. Gill, D. Denson, B. Burris, and M. Prausnitz. Effect of microneedle design on pain in human subjects. Clin. J. Pain 24:585–594 (2008).

    Google Scholar 

  19. J. Jiang, H. S. Gill, D. Ghate, B. E. McCarey, S. R. Patel, H. F. Edelhauser, and M. R. Prausnitz. Coated microneedles for drug delivery to the eye. Invest. Ophthalmol. Vis. Sci. 48:4038–4043 (2007).

    Article  PubMed  Google Scholar 

  20. P. M. Wang, M. Cornwell, J. Hill, and M. R. Prausnitz. Precise microinjection into skin using hollow microneedles. J. Invest. Dermatol. 126:1080–1087 (2006).

    Article  PubMed  CAS  Google Scholar 

  21. J. L. Bourges, S. E. Gautier, F. Delie, R. A. Bejjani, J. C. Jeanny, R. Gurny, D. BenEzra, and F. F. Behar-Cohen. Ocular drug delivery targeting the retina and retinal pigment epithelium using polylactide nanoparticles. Invest. Ophthalmol. Vis. Sci. 44:3562–3569 (2003).

    Article  PubMed  Google Scholar 

  22. M. Raspanti, M. Marchini, V. Della Pasqua, R. Strocchi, and A. Ruggeri. Ultrastructure of the extracellular matrix of bovine dura mater, optic nerve sheath and sclera. J. Anat. 181(Pt 2):181–7 (1992).

    PubMed  Google Scholar 

  23. T. W. Olsen, S. Y. Aaberg, D. H. Geroski, and H. F. Edelhauser. Human sclera: thickness and surface area. Am. J. Ophthalmol. 125:237–242 (1998).

    Article  PubMed  CAS  Google Scholar 

  24. A. Edwards, and M. R. Prausnitz. A fiber matrix model of sclera and corneal stroma for drug delivery to the eye. AIChE J. 44:214–225 (1998).

    Article  CAS  Google Scholar 

  25. K. Friedman, S. V. Pollack, T. Manning, and S. R. Pinnell. Degradation of porcine dermal connective tissue by collagenase and hyaluronidase. Br. J. Dermatol. 115:403–408 (1986).

    Article  PubMed  CAS  Google Scholar 

  26. ISTA Pharmaceuticals. Vitrase Package Insert, Irvine, CA, 2008.

  27. S. Hayasaka, S. Hara, T. Shiono, and K. Mizuno. Presence of lysosomal hyaluronidase in human corneoscleral tissue. Albrecht Von Graefes Arch. Klin. Exp. Ophthalmol. 213:235–238 (1980).

    Article  PubMed  CAS  Google Scholar 

  28. B. D. Kuppermann, E. L. Thomas, M. D. de Smet, and L. R. Grillone. Safety results of two phase III trials of an intravitreous injection of highly purified ovine hyaluronidase (Vitrase) for the management of vitreous hemorrhage. Am. J. Ophthalmol. 140:585–597 (2005).

    Article  PubMed  CAS  Google Scholar 

  29. Genentech. Lucentis Package Insert, South San Francisco, CA, 2008.

  30. M. Gibson. Pharmaceutical Preformulation and Formulation: A Practical Guide from Candidate Drug Selection to Commerical Dosage Form. Informa Healthcare, New York, 2001.

    Google Scholar 

Download references

Acknowledgements

We would like to thank Uday Kompella and Swita Raghava for providing the nanoparticles and Wijaya Martanto for helpful technical discussions. This work was carried out in the Center for Drug Design, Development and Delivery and the Institute for Bioengineering and Bioscience at Georgia Tech and was supported in part by the National Institutes of Health (NEI grant R24-EY-017045).

Author information

Authors and Affiliations

  1. School of Chemical and Biomolecular Engineering, Georgia Institute of Technology, 311 Ferst Drive, Atlanta, GA, 30332-0100, USA

    Jason Jiang, Jason S. Moore & Mark R. Prausnitz

  2. Emory Eye Center, Emory University, Atlanta, GA, 30322, USA

    Henry F. Edelhauser

Authors
  1. Jason Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jason S. Moore
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Henry F. Edelhauser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Mark R. Prausnitz
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Mark R. Prausnitz.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jiang, J., Moore, J.S., Edelhauser, H.F. et al. Intrascleral Drug Delivery to the Eye Using Hollow Microneedles. Pharm Res 26, 395–403 (2009). https://doi.org/10.1007/s11095-008-9756-3

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11095-008-9756-3

KEY WORDS

Search

Navigation