{"doi":"10.1101/2021.02.09.430012","title":"Reversible blood-brain barrier opening utilizing the membrane active peptide melittin <i>in vitro</i> and <i>in vivo</i>","abstract":"Abstract The blood-brain barrier (BBB) tightly controls entry of molecules and cells into the brain, restricting the delivery of therapeutics. Blood-brain barrier opening (BBBO) utilizes reversible disruption of cell-cell junctions between brain microvascular endothelial cells to enable transient entry into the brain. Development of BBBO techniques has been hindered by a lack of physiological models for in vitro study. Here, we utilize an in vitro tissue-engineered microvessel model to demonstrate that melittin, a membrane active peptide present in bee venom, supports BBBO. From endothelial and neuronal viability studies, we identify the accessible concentration range for BBBO. We then use a tissue-engineered model of the human BBB to optimize dosing and elucidate the mechanism of opening. Melittin and other membrane active variants transiently increase paracellular permeability via disruption of cell-cell junctions. In mice, we demonstrate a minimum clinically effective intra-arterial dose of 3 μM·min melittin, which is reversible within one day and neurologically safe. Melittin-induced BBBO represents a novel platform for delivery of therapeutics into the brain.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":223098,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9644,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":396842,"name":"Alexander Komin","orcid":"0000-0001-8480-3860","position":1,"is_corresponding":false},{"id":416232,"name":"Xiaoyan Lan","orcid":"0000-0003-4741-9426","position":2,"is_corresponding":false},{"id":665651,"name":"Jackson G. DeStefano","orcid":null,"position":3,"is_corresponding":false},{"id":416230,"name":"Chengyan Chu","orcid":"0000-0002-4486-1051","position":4,"is_corresponding":false},{"id":429880,"name":"Guanshu Liu","orcid":"0000-0002-8188-4332","position":5,"is_corresponding":false},{"id":416236,"name":"Piotr Walczak","orcid":"0000-0002-3733-3322","position":6,"is_corresponding":false},{"id":396845,"name":"Kalina Hristova","orcid":"0000-0003-4274-4406","position":7,"is_corresponding":false},{"id":267846,"name":"Peter C. Searson","orcid":"0000-0002-5417-0828","position":8,"is_corresponding":false},{"id":57485,"name":"Raleigh M. Linville","orcid":"0000-0001-6544-3150","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:54:07.287704Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}