Skip to main content
SpringerLink
Log in

Topical Drug Delivery to the Back of the Eye

  • Chapter
  • First Online:
Drug Product Development for the Back of the Eye

Part of the book series: AAPS Advances in the Pharmaceutical Sciences Series ((AAPS,volume 2))

Abstract

A topical eye drop represents the least invasive method for targeting drugs to the back of the eye. Systemic exposure and potential toxicity are minimized relative to oral drugs, and an eye drop offers a more patient-friendly experience compared to intravitreal or periocular injections. Ocular tissue barriers and clearance mechanisms render this mode of delivery relatively inefficient for most drugs, and eye drop delivery for posterior indications pose a challenging proposition. However, there are presently a number of examples of compounds in clinical development for posterior diseases of the eye. This chapter will detail our mechanistic understanding of how these drugs transit to the back of the eye.

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

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Acheampong AA, Shackleton M, John B et al (2002) Distribution of brimonidine into anterior and posterior tissues of monkey, rabbit, and rat eyes. Drug Metab Dispos 30:421–429

    Article  PubMed  CAS  Google Scholar 

  • Ahmed I, Patton TF (1985) Importance of the noncorneal absorption route in topical ophthalmic drug delivery. Invest Ophthalmol Vis Sci 26:584–587

    PubMed  CAS  Google Scholar 

  • Ahmed I, Gokhale RD, Shah MV et al (1987) Physicochemical determinants of drug diffusion across the conjunctiva, sclera, and cornea. J Pharm Sci 76:583–586

    Article  PubMed  CAS  Google Scholar 

  • Alm A, Nilsson SF (2009) Uveoscleral outflow – a review. Exp Eye Res 88:760–768

    Article  PubMed  CAS  Google Scholar 

  • Ambati J, Canakis CS, Miller JW et al (2000) Diffusion of high molecular weight compounds through sclera. Invest Ophthalmol Vis Sci 41:1181–1185

    PubMed  CAS  Google Scholar 

  • Bill A, Phillips CI (1971) Uveoscleral drainage of aqueous humour in human eyes. Exp Eye Res 12:275–281

    Article  PubMed  CAS  Google Scholar 

  • Campochiaro PA, Shah SM, Hafiz G et al (2010) Topical mecamylamine for diabetic macular edema. Am J Ophthalmol 49:839–851

    Article  Google Scholar 

  • Chung YB, Han K, Nishiura A et al (1998) Ocular absorption of Pz-peptide and its effect on the ocular and systemic pharmacokinetics of topically applied drugs in the rabbit. Pharm Res 15:1882–1887

    Article  PubMed  CAS  Google Scholar 

  • Doukas J, Mahesh S, Umeda N et al (2008) Topical administration of a multi-targeted kinase inhibitor suppresses choroidal neovascularization and retinal edema. J Cell Physiol 216:29–37

    Article  PubMed  CAS  Google Scholar 

  • Durairaj C, Shah JC, Senapati S et al (2009) Prediction of vitreal half-life based on drug physicochemical properties: quantitative structure-pharmacokinetic relationships (QSPKR). Pharm Res 26:1236–1260

    Article  PubMed  CAS  Google Scholar 

  • Furrer E, Berdugo M, Stella C (2009) Pharmacokinetics and posterior segment biodistribution of ESBA105, an anti-TNFa single-chain antibody, upon topical administration to the rabbit eye. Invest Ophthalmol Vis Sci 50:771–778

    Article  PubMed  Google Scholar 

  • Geroski DH, Edelhauser HF (2000) Drug delivery for posterior segment eye disease. Invest Ophthalmol Vis Sci 41:961–964

    PubMed  CAS  Google Scholar 

  • Geroski DH, Edelhauser HF (2001) Transscleral drug delivery for posterior segment disease. Adv Drug Deliv Rev 52:37–48

    Article  PubMed  CAS  Google Scholar 

  • Ghate D, Brooks W, McCarey BE, Edelhauser HF (2007) Pharmacokinetics of intraocular drug delivery by periocular injections using ocular fluorophotometry. Invest Ophthalmol Vis Sci 48:2230–2237

    Article  PubMed  Google Scholar 

  • Goodman A, Gilman L (2005) The pharmacological basis of therapeutics. In: Brunton L, Lazo J, Parker K (eds), 10th edn. McGraw-Hill, NY. Chapter 63 Natural Products in Cancer Chemo­therapy: Hormones and Related Agents http://accessmedicine.com/resourceTOC.aspx?resourceID=651

  • Hosoya K, Tachikawa M (2009) Inner blood-retinal barrier transporters: role of retinal drug delivery. Pharm Res 26:2055–2065

    Article  PubMed  CAS  Google Scholar 

  • Huang HS, Schoenwald RD, Lach JL (1983) Corneal penetration behavior of beta-blocking agents II: assessment of barrier contributions. J Pharm Sci 72:1272–1279

    Article  PubMed  CAS  Google Scholar 

  • Hughes PM, Olejnik O, Chang-Lin JE et al (2005) Topical and systemic drug delivery to the posterior segments. Adv Drug Deliv Rev 57:2010–2032

    Article  PubMed  CAS  Google Scholar 

  • Kent AR, Nussdorf JD, David R et al (2001) Vitreous concentration of topically applied brimonidine tartrate 0.2%. Ophthalmology 108:784–787

    Article  PubMed  CAS  Google Scholar 

  • Kiuchi K, Matsuoka M, Wu JC et al (2008) Mecamylamine suppresses Basal and nicotine-stimulated choroidal neovascularization. Invest Ophthalmol Vis Sci 49:1705–1711

    Article  PubMed  Google Scholar 

  • Koeberle MJ, Hughes PM, Skellern GG et al (2006) Pharmacokinetics and disposition of memantine in the arterially perfused bovine eye. Pharm Res 23:2781–2798

    Article  PubMed  CAS  Google Scholar 

  • Lichtlen PD, Lam T, Nork M et al (2010) Relative contribution of VEGF and TNFa in the cynomolgus laser-induced CNV model: comparing efficacy of bevacizumab, adalimumab and ESBA105. Invest Ophthalmol Vis Sci 51:4738–4745

    Google Scholar 

  • Lipinski CA, Lombardo F, Dominy BW et al (2001) Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv Drug Deliv Rev 46:3–26

    Article  PubMed  CAS  Google Scholar 

  • Mannermaa E, Vellonen KS, Urtti A (2006) Drug transport in corneal epithelium and blood-retina barrier: emerging role of transporters in ocular pharmacokinetics. Adv Drug Deliv Rev 58:1136–1163

    Article  PubMed  CAS  Google Scholar 

  • Mizuno K, Koide T, Saito N et al (2002) Topical nipradilol: effects on optic nerve head circulation in humans and periocular distribution in monkeys. Invest Ophthalmol Vis Sci 43:3243–3250

    PubMed  Google Scholar 

  • Mizuno K, Koide T, Shimada S et al (2009) Route of penetration of topically instilled nipradilol into the ipsilateral posterior retina. Invest Ophthalmol Vis Sci 50:2839–2847

    Article  PubMed  Google Scholar 

  • Ottiger M, Thiel MA, Feige U et al (2009) Efficient intraocular penetration of topical anti-TNFa single-chain antibody (ESBA105) to anterior and posterior segment without penetration enhancer. Invest Ophthalmol Vis Sci 50:779–786

    Article  PubMed  Google Scholar 

  • Pade V, Stavchansky S (1997) Estimation of the relative contribution of the transcellular and paracellular pathway to the transport of passively absorbed drugs in the Caco-2 cell culture model. Pharmacol Res 14:1210–1215

    Article  CAS  Google Scholar 

  • Palanki MS, Akiyama H, Campochiaro P et al (2008) Development of prodrug 4-chloro-3-(5-methyl-3-{[4-(2-pyrrolidin-1-ylethoxy)phenyl]amino}-1,2,4-benzotria zin-7-yl)phenyl benzoate (TG100801): a topically administered therapeutic candidate in clinical trials for the treatment of age-related macular degeneration. J Med Chem 51:1546–1559

    Article  PubMed  CAS  Google Scholar 

  • Rao VR, Prescott E, Shelke NB et al (2010) Delivery of SAR 1118 to retina via ophthalmic drops and its effectiveness in reduction of retinal leukostasis and vascular leakiness in rat streptozotocin (STZ) model of diabetic retinopathy (DR). Invest Ophthalmol Vis Sci 51:5198–5204

    Google Scholar 

  • Reed KK (2008) Diseases of the lacrimal system. In: Bartlett JD, Jaanus SD (eds) Clinical ocular pharmacology, 5th edn. Butterworth, St. Louis, pp 415–435

    Chapter  Google Scholar 

  • Rojanasakul Y, Robinson JR (1991) The cytoskeleton of the cornea and its role in tight junction permeability. Int J Pharm 68:135–149

    Article  CAS  Google Scholar 

  • Scheppke L, Aguilar E, Gariano RF et al (2008) Retinal vascular permeability suppression by topical application of a novel VEGFR2/Src kinase inhibitor in mice and rabbits. J Clin Invest 118:2337–2346

    PubMed  CAS  Google Scholar 

  • Stjernschantz J, Selén G, Astin M et al (1999) Effect of latanoprost on regional blood flow and capillary permeability in the monkey eye. Arch Ophthalmol 117:1363–1367

    PubMed  CAS  Google Scholar 

  • Struble C, Choinski R, Martin M (2007) Ocular and systemic distribution, and excretion of radioactivity following topical ocular administration of 14C-TG100801 to pigmented rabbits. Acta Ophthalmol Scand 85(s240):0–0

    Google Scholar 

  • Thiel MA, Coster DJ, Standfield SD et al (2002) Penetration of engineered antibody fragments into the eye. Clin Exp Immunol 128:67–74

    Article  PubMed  CAS  Google Scholar 

  • Tojo K (1988) Pharmacokinetic model of transcorneal drug delivery. Math Biosci 89:53–77

    Article  Google Scholar 

  • Wang BG, König K, Halbhuber KJ (2010) Two-photon microscopy of deep intravital tissues and its merits in clinical research. J Microsc 238:1–20

    Article  PubMed  CAS  Google Scholar 

  • Williams KA, Brereton HM, Farrall A et al (2005) Topically applied antibody fragments penetrate into the back of the rabbit eye. Eye (Lond) 19:910–913

    CAS  Google Scholar 

  • Wong WT, Kam W, Cunningham D et al (2010) Treatment of geographic atrophy by the topical administration of OT-551: results of a phase II clinical trial. Invest Ophthalmol Vis Sci 51:6131–6139

    Google Scholar 

  • Zhang X, Kengatharan M, Cooke JP et al (2007) Topical mecamylamine formulations for ocular administration and uses thereof. Int Patent App WO/2007/075720

    Google Scholar 

  • Zhang T, Xiang CD, Gale D et al (2008) Drug transporter and cytochrome P450 mRNA expression in human ocular barriers: implications for ocular drug disposition. Drug Metab Dispos 36:1300–1307

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. OphthaMystic Consulting, Oakland, CA, USA

    Thomas Gadek PhD

  2. Ophthiris, GlaxoSmithKline Pharmaceuticals, King of Prussia, PA, USA

    Dennis Lee PhD

Authors
  1. Thomas Gadek PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dennis Lee PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Thomas Gadek PhD .

Editor information

Editors and Affiliations

  1. School of Pharmacy, University of Colorado Denver, East 17th Avenue 12631, Aurora, 80045, Colorado, USA

    Uday B. Kompella

  2. School of Medicine, Emory University, Clifton Road NE., 1365, Atlanta, 30322, Georgia, USA

    Henry F. Edelhauser

Rights and permissions

Reprints and permissions

Copyright information

© 2011 American Association of Pharmaceutical Scientists

About this chapter

Cite this chapter

Gadek, T., Lee, D. (2011). Topical Drug Delivery to the Back of the Eye. In: Kompella, U., Edelhauser, H. (eds) Drug Product Development for the Back of the Eye. AAPS Advances in the Pharmaceutical Sciences Series, vol 2. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-9920-7_5

Download citation

Publish with us

Policies and ethics

Societies and partnerships

Search

Navigation