Overcoming the blood-brain barrier for therapeutics targeting neurodegenerative diseases: a patent review (2020-present).

INTRODUCTION: The blood-brain barrier (BBB) restricts drug entry into the CNS, with most therapeutics showing < 1% brain penetration, limiting efficacy in neurodegenerative diseases. AREAS COVERED: Patents (2020-2026) were retrieved from SciFinder, Web of Science, PubMed, and Reaxys using combinations of 'blood-brain barrier,' 'brain delivery,' and neurodegenerative disease terms. Technologies were included if supported by in vitro or in vivo BBB‑penetration evidence for neurodegenerative indications; purely computational, non‑English untranslated, and non‑targeted conventional formulation patents were excluded. Eligible patents were classified into protein/antibody‑based, small molecule, nanocarrier, physical‑assisted, permeability enhancer, and emerging technology categories. EXPERT OPINION: Receptormedia-ted transcytosis, dual-targeting ligands, and ultrasound opening are enhancing delivery precision; emerging systems (small molecules, peptides, nanozymes) combine penetration with target inhibition, overcoming traditional bottlenecks and accelerating clinical translation.