{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T09:17:37Z","timestamp":1785403057813,"version":"3.56.0"},"reference-count":40,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T00:00:00Z","timestamp":1774396800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Center for Protein Therapeutics at the University of Buffalo"},{"id":[{"id":"https:\/\/ror.org\/01y64my43","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000071","name":"Eunice Kennedy Shriver National Institute of Child Health and Human Development","doi-asserted-by":"publisher","award":["P30HD106451"],"award-info":[{"award-number":["P30HD106451"]}],"id":[{"id":"10.13039\/100000071","id-type":"DOI","asserted-by":"publisher"}]},{"award":["P30HD106451"],"award-info":[{"award-number":["P30HD106451"]}],"id":[{"id":"https:\/\/ror.org\/04byxyr05","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM114179"],"award-info":[{"award-number":["GM114179"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"crossref","award":["GM146097"],"award-info":[{"award-number":["GM146097"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"crossref"}]},{"award":["GM114179"],"award-info":[{"award-number":["GM114179"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"award":["GM146097"],"award-info":[{"award-number":["GM146097"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000060","name":"National Institute of Allergy and Infectious Diseases","doi-asserted-by":"publisher","award":["AI138195"],"award-info":[{"award-number":["AI138195"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"award":["AI138195"],"award-info":[{"award-number":["AI138195"]}],"id":[{"id":"https:\/\/ror.org\/043z4tv69","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Cancer Institute","award":["R01CA246785"],"award-info":[{"award-number":["R01CA246785"]}]},{"name":"National Cancer Institute","award":["R01CA256928"],"award-info":[{"award-number":["R01CA256928"]}]},{"name":"National Cancer Institute","award":["R01CA275967"],"award-info":[{"award-number":["R01CA275967"]}]},{"award":["R01CA246785"],"award-info":[{"award-number":["R01CA246785"]}],"id":[{"id":"https:\/\/ror.org\/02t771148","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA256928"],"award-info":[{"award-number":["R01CA256928"]}],"id":[{"id":"https:\/\/ror.org\/02t771148","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA275967"],"award-info":[{"award-number":["R01CA275967"]}],"id":[{"id":"https:\/\/ror.org\/02t771148","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibodies"],"abstract":"<jats:p>Background\/Objectives: The neonatal Fc receptor (FcRn) plays a crucial role in extending the systemic half-life of monoclonal antibodies (mAbs), but its influence on ocular distribution remains incompletely understood. This study investigated the impact of FcRn on the ocular disposition of mAbs following systemic administration in rabbits. Methods: New Zealand White rabbits received a single intravenous dose (1 mg\/kg) of either wild-type trastuzumab (TS-WT) or its FcRn non-binding variant (IHH). Plasma and ocular tissues (retina, iris\u2013ciliary body, vitreous humor, aqueous humor, cornea, conjunctiva, and tears) were collected at terminal time points up to 336 h for TS-WT and 168 h for IHH. Antibody concentrations were quantified using a validated sandwich ELISA. Pharmacokinetic parameters and antibody biodistribution coefficients (ABC) were calculated to assess the FcRn-mediated effects on ocular distribution. Results: TS-WT demonstrated 2-fold higher systemic exposure compared to IHH. The iris\u2013ciliary body exhibited the highest absolute exposure for both antibodies, with TS-WT showing significantly higher accumulation (ABC0\u2013168h: 14.95% vs. 8.89%). Retinal distribution remained comparable between antibodies (5.96% vs. 5.51%). Both antibodies were detectable in tears, with ABC value of ~4% reported for TS-WT. TS-WT also demonstrated markedly increased distribution in vitreous humor and tear fluid (3.5- and 5.5-fold higher ABC values, respectively) compared to IHH. The cornea (5.76% vs. 5.57%) and conjunctiva (7.71% vs. 7.21%) showed comparable relative distribution between TS-WT and IHH, while aqueous humor showed minimal differences (0.44% vs. 0.52%). Conclusions: This investigation reveals distinct tissue-specific patterns of FcRn-mediated mAb distribution within the eye. FcRn binding significantly enhanced antibody distribution in ocular tissues, such as the iris\u2013ciliary body, and tears, with less pronounced effects on the retina, cornea, conjunctiva and aqueous humor. These findings provide mechanistic insights for optimizing mAb-based therapeutics for ocular disease and understanding the ocular toxicity of mAb-based therapeutics, such as antibody\u2013drug conjugates.<\/jats:p>","DOI":"10.3390\/antib15020027","type":"journal-article","created":{"date-parts":[[2026,3,25]],"date-time":"2026-03-25T09:11:14Z","timestamp":1774429874000},"page":"27","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["The Effect of FcRn Binding on Ocular Disposition of Monoclonal Antibodies"],"prefix":"10.3390","volume":"15","author":[{"given":"Sanika","family":"Naware","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214-8033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saurav","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214-8033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sahil","family":"Salvi","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214-8033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dhvani","family":"Patel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214-8033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0723-6206","authenticated-orcid":false,"given":"Dhaval K.","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy and Pharmaceutical Sciences, The State University of New York at Buffalo, Buffalo, NY 14214-8033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,25]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Jairam, R.K., Franz, M., Hanke, N., and Kuepfer, L. 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