{"doi":"10.3390/pharmaceutics15051357","title":"Permeability of Metformin across an In Vitro Blood–Brain Barrier Model during Normoxia and Oxygen-Glucose Deprivation Conditions: Role of Organic Cation Transporters (Octs)","abstract":"Our lab previously established that metformin, a first-line type two diabetes treatment, activates the Nrf2 pathway and improves post-stroke recovery. Metformin's brain permeability value and potential interaction with blood-brain barrier (BBB) uptake and efflux transporters are currently unknown. Metformin has been shown to be a substrate of organic cationic transporters (Octs) in the liver and kidneys. Brain endothelial cells at the BBB have been shown to express Octs; thus, we hypothesize that metformin uses Octs for its transport across the BBB. We used a co-culture model of brain endothelial cells and primary astrocytes as an in vitro BBB model to conduct permeability studies during normoxia and hypoxia using oxygen-glucose deprivation (OGD) conditions. Metformin was quantified using a highly sensitive LC-MS/MS method. We further checked Octs protein expression using Western blot analysis. Lastly, we completed a plasma glycoprotein (P-GP) efflux assay. Our results showed that metformin is a highly permeable molecule, uses Oct1 for its transport, and does not interact with P-GP. During OGD, we found alterations in Oct1 expression and increased permeability for metformin. Additionally, we showed that selective transport is a key determinant of metformin's permeability during OGD, thus, providing a novel target for improving ischemic drug delivery.","journal":"Pharmaceutics","year":2023,"id":320575,"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":48,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9591,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":949237,"name":"Yong Zhang","orcid":"0000-0001-6577-5235","position":1,"is_corresponding":false},{"id":1031726,"name":"Khondker Ayesha Akter","orcid":null,"position":2,"is_corresponding":false},{"id":464460,"name":"Saeideh Nozohouri","orcid":null,"position":3,"is_corresponding":false},{"id":260322,"name":"Sabrina Rahman Archie","orcid":"0000-0003-3021-0079","position":4,"is_corresponding":false},{"id":921489,"name":"Dhaval Patel","orcid":"0000-0002-6959-3487","position":5,"is_corresponding":false},{"id":463174,"name":"Heidi Villalba","orcid":"0000-0003-0915-5271","position":6,"is_corresponding":false},{"id":463176,"name":"Thomas J. Abbruscato","orcid":"0000-0001-7597-9477","position":7,"is_corresponding":false},{"id":677122,"name":"Sejal Sharma","orcid":"0000-0001-5923-2613","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:07:22.377587Z","pmid":"37242599","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":[]}