{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:08:59Z","timestamp":1792789739503,"version":"4.5.0"},"reference-count":266,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100008425","name":"Conseller\u00eda de Cultura, Educaci\u00f3n e Universidade","doi-asserted-by":"publisher","award":["ED481B-2023\u2013092"],"award-info":[{"award-number":["ED481B-2023\u2013092"]}],"id":[{"id":"10.13039\/501100008425","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ED481B-2023\u2013092"],"award-info":[{"award-number":["ED481B-2023\u2013092"]}],"id":[{"id":"https:\/\/ror.org\/03gq5rs15","id-type":"ROR","asserted-by":"publisher"}]},{"name":"MICINN","award":["PID2022-142350OB-C21"],"award-info":[{"award-number":["PID2022-142350OB-C21"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"crossref"}]},{"award":["PID2022-142350OB-C21"],"award-info":[{"award-number":["PID2022-142350OB-C21"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010801","name":"Xunta de Galicia","doi-asserted-by":"publisher","award":["ED431C 2025\/08"],"award-info":[{"award-number":["ED431C 2025\/08"]}],"id":[{"id":"10.13039\/501100010801","id-type":"DOI","asserted-by":"publisher"}]},{"award":["ED431C 2025\/08"],"award-info":[{"award-number":["ED431C 2025\/08"]}],"id":[{"id":"https:\/\/ror.org\/0181xnw06","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Homocystinuria type CblC is a congenital error in cobalamin metabolism characterized by increased homocysteine and methylmalonic acid levels, together with a reduced methionine availability. This metabolic imbalance leads to multisystemic pathologies, including ophthalmic pathologies that cause damage to the photoreceptors and oculomotor disorders, such as pigmentary retinopathy and nystagmus, respectively. Current commercial treatment (Megamilbedoce\u00ae) is mainly based on intramuscular hydroxocobalamin administration. Although this approach may improve systemic manifestations, it is ineffective at the ophthalmic level. Given the ophthalmic complications, there is a clear need for new therapeutic strategies capable of significantly reaching the eyeball, improving visual function and patient quality of life. The most convenient and acceptable route for patients is topical\u2013ophthalmic administration. However, treatments administered by this route have significant limitations due to anatomical and physiological ophthalmic barriers. In this context, advanced ophthalmic drug delivery systems have gained increasing interest as strategies to address the low ocular bioavailability of conventional treatments. By increasing ocular residence time, limiting drug loss through tear turnover and nasolacrimal drainage, and improving interaction with ocular tissues, these platforms may enhance local drug availability and therapeutic performance. Nanoparticles, lipid-based carriers, hydrogels, in situ gelling systems, surfactant-based formulations and other multifunctional delivery approaches have shown potential to improve drug retention, tissue penetration and controlled release within the ocular environment. Although reaching posterior ocular tissues through topical administration remains a major pharmacological challenge, these technologies open new possibilities for developing less invasive and more effective treatments for the ocular manifestations of CblC-type homocystinuria.<\/jats:p>","DOI":"10.3390\/pharmaceutics18091182","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T08:03:47Z","timestamp":1789977827000},"page":"1182","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Advanced Ophthalmic Drug Delivery in Homocystinuria Type CblC: A Translational Review of Ophthalmic Pathologies and Therapeutic Opportunities"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-3370-4997","authenticated-orcid":false,"given":"Selene","family":"Cuello-Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), 15705 Santiago de Compostela, Spain"},{"name":"Institute of Materials (iMATUS), University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Spain"},{"name":"Paraquasil Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martina","family":"Sanna","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), 15705 Santiago de Compostela, Spain"},{"name":"Institute of Materials (iMATUS), University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Spain"},{"name":"Paraquasil Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Imelda","family":"Lecoeuche","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), 15705 Santiago de Compostela, Spain"},{"name":"Institute of Materials (iMATUS), University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Spain"},{"name":"Paraquasil Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Sarmento","sequence":"additional","affiliation":[{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 42000-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9030-2253","authenticated-orcid":false,"given":"Francisco J.","family":"Otero-Espinar","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), 15705 Santiago de Compostela, Spain"},{"name":"Institute of Materials (iMATUS), University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Spain"},{"name":"Paraquasil Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0107-1292","authenticated-orcid":false,"given":"Victoria","family":"D\u00edaz-Tom\u00e9","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacy and Pharmaceutical Technology, University of Santiago de Compostela (USC), 15705 Santiago de Compostela, Spain"},{"name":"Institute of Materials (iMATUS), University of Santiago de Compostela (USC), 15706 Santiago de Compostela, Spain"},{"name":"Paraquasil Group, University Clinical Hospital, Health Research Institute of Santiago de Compostela (IDIS), 15706 Santiago de Compostela, Spain"},{"name":"Instituto de Investiga\u00e7\u00e3o e Inova\u00e7\u00e3o em Sa\u00fade (i3S), Universidade do Porto, 42000-135 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"17040","DOI":"10.1038\/nrdp.2017.40","article-title":"Vitamin B12 deficiency","volume":"3","author":"Green","year":"2017","journal-title":"Nat. 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