{"title":"Beyond the blood-brain barrier: the fate of transcytosed therapeutics.","authors":"Habib Baghirov","doi":"10.1016/j.tips.2025.08.006","DOIUrl":null,"url":null,"abstract":"<p><p>Transcytosis across the blood-brain barrier (BBB) enables systemically administered large therapeutics to reach the brain parenchyma, but their fate in the parenchyma ultimately governs their therapeutic effect. Recent studies show that brain parenchymal cell uptake, internalization kinetics, reuptake at the BBB, and diffusion in the brain parenchyma shape the distribution and retention of therapeutics. Target engagement further influences their behavior beyond the BBB. These insights have prompted new strategies to enhance their distribution, retention, and target engagement. These include the selection of transport targets with favorable trafficking properties, the use of anchoring proteins, and modeling-based optimization. This opinion highlights emerging understanding of the fate of therapeutics in the brain parenchyma and outlines strategies to optimize this fate.</p>","PeriodicalId":23250,"journal":{"name":"Trends in pharmacological sciences","volume":" ","pages":"946-957"},"PeriodicalIF":19.9000,"publicationDate":"2025-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Trends in pharmacological sciences","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/j.tips.2025.08.006","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/9/19 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
引用次数: 0
Abstract
Transcytosis across the blood-brain barrier (BBB) enables systemically administered large therapeutics to reach the brain parenchyma, but their fate in the parenchyma ultimately governs their therapeutic effect. Recent studies show that brain parenchymal cell uptake, internalization kinetics, reuptake at the BBB, and diffusion in the brain parenchyma shape the distribution and retention of therapeutics. Target engagement further influences their behavior beyond the BBB. These insights have prompted new strategies to enhance their distribution, retention, and target engagement. These include the selection of transport targets with favorable trafficking properties, the use of anchoring proteins, and modeling-based optimization. This opinion highlights emerging understanding of the fate of therapeutics in the brain parenchyma and outlines strategies to optimize this fate.
期刊介绍：
Trends in Pharmacological Sciences (TIPS) is a monthly peer-reviewed reviews journal that focuses on a wide range of topics in pharmacology, pharmacy, pharmaceutics, and toxicology. Launched in 1979, TIPS publishes concise articles discussing the latest advancements in pharmacology and therapeutics research.
The journal encourages submissions that align with its core themes while also being open to articles on the biopharma regulatory landscape, science policy and regulation, and bioethics.
Each issue of TIPS provides a platform for experts to share their insights and perspectives on the most exciting developments in the field. Through rigorous peer review, the journal ensures the quality and reliability of published articles.
Authors are invited to contribute articles that contribute to the understanding of pharmacology and its applications in various domains. Whether it's exploring innovative drug therapies or discussing the ethical considerations of pharmaceutical research, TIPS provides a valuable resource for researchers, practitioners, and policymakers in the pharmacological sciences.
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