{"doi":"10.1002/smll.202207278","title":"A Highly Translatable Dual‐arm Local Delivery Strategy To Achieve Widespread Therapeutic Coverage in Healthy and Tumor‐bearing Brain Tissues","abstract":"Drug delivery nanoparticles (NPs) based entirely on materials generally recognized as safe that provide widespread parenchymal distribution following intracranial administration via convection-enhanced delivery (CED) are introduced. Poly(lactic-co-glycolic acid) (PLGA) NPs are coated with various poloxamers, including F68, F98, or F127, via physical adsorption to render particle surfaces non-adhesive, thereby resisting interactions with brain extracellular matrix. F127-coated PLGA (F127/PLGA) NPs provide markedly greater distribution in healthy rat brains compared to uncoated NPs and widespread coverage in orthotopically-established brain tumors. Distribution analysis of variously-sized F127/PLGA NPs determines the average rat brain tissue porosity to be between 135 and 170 nm while revealing unprecedented brain coverage of larger F127/PLGA NPs with an aid of hydraulic pressure provided by CED. Importantly, F127/PLGA NPs can be lyophilized for long-term storage without compromising their ability to penetrate the brain tissue. Further, 65- and 200-nm F127/PLGA NPs lyophilized-reconstituted and administered in a moderately hyperosmolar infusate solution show further enhance particle dissemination in the brain via osmotically-driven enlargement of the brain tissue porosity. Combination of F127/PLGA NPs and osmotic tissue modulation provides a means with a clear regulatory path to maximize the brain distribution of large NPs that enable greater drug loading and prolong drug release.","journal":"Small","year":2023,"id":347334,"datarank":0.37273599746820013,"base_score":2.4849066497880004,"endowment":2.4849066497880004,"self_citation_contribution":0.37273599746820013,"citation_network_contribution":0.0,"self_endowment_contribution":0.37273599746820013,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":11,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9517,"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":703830,"name":"Gijung Kwak","orcid":"0000-0001-6908-9638","position":1,"is_corresponding":false},{"id":1088825,"name":"Heng Wang","orcid":"0009-0001-0197-7767","position":2,"is_corresponding":false},{"id":1088826,"name":"Haolin Li","orcid":"0009-0003-1613-5110","position":3,"is_corresponding":false},{"id":564769,"name":"Yiting Huang","orcid":"0000-0001-9590-6005","position":4,"is_corresponding":false},{"id":1089210,"name":"Shun‐Wen Chen","orcid":null,"position":5,"is_corresponding":false},{"id":326901,"name":"Betty Tyler","orcid":"0000-0001-9800-6969","position":6,"is_corresponding":false},{"id":232275,"name":"Charles G. Eberhart","orcid":"0000-0002-2910-9427","position":7,"is_corresponding":false},{"id":269610,"name":"Justin Hanes","orcid":null,"position":8,"is_corresponding":false},{"id":428977,"name":"Jung Soo Suk","orcid":"0000-0002-2437-0001","position":9,"is_corresponding":false},{"id":428974,"name":"Karina Negrón","orcid":"0000-0002-5376-7657","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:11:57.720122Z","pmid":"36651002","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":[]}