Pharmacokinetics of Monoclonal Antibody and Antibody Fragments in the Mouse Eye Following Systemic Administration
Open accessAbstract
The ocular pharmacokinetics (PK) of antibody-based therapies are infrequently studied in mice due to the technical difficulties in working with the small murine eye. This study is the first of its kind to quantitatively measure the PK of variously sized proteins in the plasma, cornea/ICB, vitreous humor, retina, and posterior cup (including choroid) of the mouse and to evaluate the relationship between molecular weight (MW) and antibody biodistribution coefficient (BC) to the eye. Proteins analyzed include trastuzumab (150 kDa), trastuzumab-vc-MMAE (T-vc-MMAE, 155 kDa), F(ab)2 (100 kDa), Fab (50 kDa), and scFv (27 kDa). As expected, ocular PK mirrored the systemic PK as plasma was the driving force for ocular exposure. For trastuzumab, T-vc-MMAE, F(ab)2, Fab, and scFv, respectively, the BCs in the cornea/ICB were 0.610%, 0.475%, 1.74%, 3.39%, and 13.7%; the BCs in the vitreous humor were 0.0198%, 0.0427%, 0.0934%, 0.234%, and 5.56%; the BCs for the retina were 0.539%, 0.230%, 0.704%, 2.44%, and 20.4%; the BCs for the posterior cup were 0.557%, 0.650%, 1.47%, 4.06%, and 13.9%. The relationship between BC and MW was best characterized by a log-log regression in which BC decreased as MW increased, with every doubling in MW leading to a decrease in BC by a factor of 3.44 × , 6.76 × , 4.74 × , and 3.43 × in cornea/ICB, vitreous humor, retina, and posterior cup, respectively. In analyzing the disposition of protein therapeutics to the eye, these findings enhance our understanding of the potential for ocular toxicity of systemically administered protein therapeutics and may aid in the discovery of systemically administered protein therapeutics for ocular disorders.
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The blood-ocular barrier restricts passage of systemic antibodies into the intraocular space, although its functionality can be compromised in certain disease states.
“The blood-ocular barrier restricts the passage of systemic antibodies into the intraocular space,26 although the functionality of this barrier can be compromised in certain disease states.27”
From Nonclinical study of ixo-vec gene therapy for nAMD supports efficacy for a human dose of 6E10 vg/eye and staggered dosing of fellow eyes (2025) · cites this paper as [26]
Access of systemic antibodies and other macromolecules to the intraocular space is not completely restricted.
“Published evidence indicates that the access of systemic antibodies and other macromolecules to the intraocular space is not completely restricted.26”
From Nonclinical study of ixo-vec gene therapy for nAMD supports efficacy for a human dose of 6E10 vg/eye and staggered dosing of fellow eyes (2025) · cites this paper as [26]
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“The blood-ocular barrier restricts the passage of systemic antibodies into the intraocular space, 26 although the functionality of this barrier can be compromised in certain disease states.”
- Authors
- Bussing, D., Li, Z., Li, Y., Chang, H.-P., Chang, H.-Y., Guo, L., Verma, A., & Shah, D. K.
- Affiliations
- University at Buffalo, State University of New York (US)
- Corresponding author
- Shah, Dhaval K.
- Venue
- The AAPS Journal
- Published
- 2021-11-08
- Volume
- 23
- Issue
- 6
- Pages
- 116-116
- ISSN
- 1550-7416 (ISSN-L)
- PMC
- PMC8575492
- OpenAlex
- W3213545925
- Cited by
- 16
- References
- 49
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 3 · 2023: 2 · 2022: 1
- FWCI
- 0.79
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The AAPS Journal (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University at Buffalo
- National Cancer Institute (R01CA246785)
- National Institute of General Medical Sciences (R01GM114179)
- National Institute of Allergy and Infectious Diseases (R21AI138195)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmaceutical Science › Advanced Drug Delivery Systems
- Health Sciences › Medicine › Ophthalmology › Drug-Induced Ocular Toxicity
- Keywords
- ocular pharmacokinetics, monoclonal antibodies, antibody fragments, trastuzumab, F(ab')2 fragments, FAB, scFv, molecular weight, vitreous humor, cornea, retina, choroid, ocular toxicity, therapeutic proteins, mouse eye, intracameral injection, ocular drug delivery
- MeSH terms
- Trastuzumab, Animals, Eye, Immunoglobulin Fragments, Immunoglobulin Fab Fragments, Mice, Inbred C57BL, Mice, Nude, Molecular Weight, Oligopeptides, Tissue Distribution, Immunoconjugates, Mice
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