Pharmacokinetic aspects of retinal drug delivery

del Amo, Eva M.; Rimpelä, Anna-Kaisa; Heikkinen, Emma; Kari, Otto K.; Ramsay, Eva; Lajunen, Tatu; Schmitt, Mechthild; Pelkonen, Laura; Bhattacharya, Madhushree; Richardson, Dominique; Subrizi, Astrid; Turunen, Tiina; Reinisalo, Mika; Itkonen, Jaakko; Toropainen, Elisa; Casteleijn, Marco; Kidron, Heidi; Antopolsky, Maxim; Vellonen, Kati-Sisko; Ruponen, Marika; Urtti, Arto

doi:10.1016/j.preteyeres.2016.12.001

Cited by 693Advanced Drug Delivery SystemsRetinal Diseases and TreatmentsOcular Infections and Treatments

Pharmacokinetic aspects of retinal drug delivery

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del Amo, Eva M., Rimpelä, Anna-Kaisa, Heikkinen, Emma, Kari, Otto K., Ramsay, Eva, Lajunen, Tatu, Schmitt, Mechthild, Pelkonen, Laura +13 more·2017·Progress in Retinal and Eye Research

DOI 10.1016/j.preteyeres.2016.12.001

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Abstract

Drug delivery to the posterior eye segment is an important challenge in ophthalmology, because many diseases affect the retina and choroid leading to impaired vision or blindness. Currently, intravitreal injections are the method of choice to administer drugs to the retina, but this approach is applicable only in selected cases (e.g. anti-VEGF antibodies and soluble receptors). There are two basic approaches that can be adopted to improve retinal drug delivery: prolonged and/or retina targeted delivery of intravitreal drugs and use of other routes of drug administration, such as periocular, suprachoroidal, sub-retinal, systemic, or topical. Properties of the administration route, drug and delivery system determine the efficacy and safety of these approaches. Pharmacokinetic and pharmacodynamic factors determine the required dosing rates and doses that are needed for drug action. In addition, tolerability factors limit the use of many materials in ocular drug delivery. This review article provides a critical discussion of retinal drug delivery, particularly from the pharmacokinetic point of view. This article does not include an extensive review of drug delivery technologies, because they have already been reviewed several times recently. Instead, we aim to provide a systematic and quantitative view on the pharmacokinetic factors in drug delivery to the posterior eye segment. This review is based on the literature and unpublished data from the authors' laboratory.

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Drugs are eliminated from the vitreous cavity via blood-ocular barriers and aqueous humor outflow to the systemic blood circulation.
“Drugs are eliminated from the vitreous cavity via blood–ocular barriers and aqueous humor outflow to the systemic blood circulation (del Amo et al., 2017).”
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The inner BRB is only permeable to molecules with a small diameter or molecular weight (i.e., up to 2 nanometres or a few hundred daltons).
“The inner BRB is only permeable to molecules with a small diameter or molecular weight (i.e., up to 2 nanometres or a few hundred daltons) [228]”
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The blood-retinal barrier (BRB) may impede the diffusion of molecules from the systemic circulation to the retina.
“The blood–retinal barrier (BRB)—comprising the tight junctional complexes between retinal capillary endothelial cells (inner BRB) and retinal pigment epithelial cells (outer BRB)—may also impede the diffusion of molecules from the systemic circulation to the retina.”
From Bruch’s Membrane: A Key Consideration with Complement-Based Therapies for Age-Related Macular Degeneration (2023) · cites this paper as [228]

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Authors: del Amo, E. M., Rimpelä, A.-K., Heikkinen, E., Kari, O. K., Ramsay, E., Lajunen, T., Schmitt, M., Pelkonen, L., Bhattacharya, M., Richardson, D., Subrizi, A., Turunen, T., Reinisalo, M., Itkonen, J., Toropainen, E., Casteleijn, M., Kidron, H., Antopolsky, M., Vellonen, K.-S., Ruponen, M., & Urtti, A.
Affiliations: University of Helsinki (FI)
University of Eastern Finland (FI)
ORCID: Rimpelä, Anna-Kaisa
Heikkinen, Emma
Kari, Otto K.
Ramsay, Eva
Lajunen, Tatu
Pelkonen, Laura
Bhattacharya, Madhushree
Subrizi, Astrid
Reinisalo, Mika
Itkonen, Jaakko
Toropainen, Elisa
Casteleijn, Marco
Kidron, Heidi
Vellonen, Kati-Sisko
Ruponen, Marika
Urtti, Arto
Venue: Progress in Retinal and Eye Research
Publisher: Elsevier BV
Published: 2017-03
Volume: 57
Pages: 134-185
ISSN: 1350-9462 (ISSN-L)
DOI: 10.1016/j.preteyeres.2016.12.001
OpenAlex: W2567416294
Cited by: 693
References: 476
Citations by year: 2026: 68 · 2025: 96 · 2024: 76 · 2023: 92 · 2022: 74 · 2021: 94 · 2020: 81 · 2019: 59 · 2018: 34 · 2017: 18 · 2012: 1
FWCI: 3.13
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-nd
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
creativecommons.org/licenses/by-nc-nd/4.0/ (vor)
Locations: Progress in Retinal and Eye Research (publishedVersion, cc-by-nc-nd)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (publishedVersion, other-oa)
UEF eRepo (University of Eastern Finland) (submittedVersion)
Työväentutkimus Vuosikirja (submittedVersion)
Funders: Sigrid Juséliuksen Säätiö (64578)
Itä-Suomen Yliopisto
Academy of Finland (263573, 263615, 268868, 272597, 283721)
Tekes (637/31/2015 TEKES)
Seventh Framework Programme
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
Health Sciences › Medicine › Ophthalmology › Retinal Diseases and Treatments
Health Sciences › Medicine › Ophthalmology › Ocular Infections and Treatments
Keywords: retinal drug delivery, pharmacokinetics, intravitreal injection, systemic drug delivery, topical ocular drug delivery, targeted drug delivery, dosage, tolerability, ocular drug delivery systems
MeSH terms: Animals, Humans, Retina, Retinal Diseases, Tissue Distribution, Drug Delivery Systems, Angiogenesis Inhibitors, Intravitreal Injections

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