{"doi":"10.1016/j.jconrel.2025.113963","title":"High-velocity delivery of biologics via the gastrointestinal tract by self-pressurized oral capsules","abstract":"Biologic drugs have transformed medicine, but are limited by their need for administration by injection. To enable oral delivery of biologics, we propose convective force as a physical method to overcome the barriers of the gastrointestinal tract (GIT). We designed oral capsules that self-pressurize in the GIT, mechanically fail at a specific pressure (100-170 kPa), and eject lyophilized drug with sufficient velocity to penetrate the mucosal barrier. This oral, self-pressurized aerosol (OSPRAE) was produced by a coated gelatin capsule filled with pressure-generating effervescent excipients (sodium bicarbonate, citric acid) and drug in a biodegradable polymer chamber (poly(lactic acid)). After initial optimization in vitro, OSPRAE allowed for insulin delivery to surgically exposed intestinal mucosa in vivo with similar pharmacokinetics and pharmacodynamics to subcutaneous injection in rats, despite lower bioavailability. Histological analysis showed only superficial damage to the intestinal epithelium that was highly localized to the microscopic area of impact. Future studies should administer OSPRAE orally to larger animals and, ultimately, to humans. The OSPRAE capsule offers a novel method to increase delivery of biologics across the intestinal mucosa using convective force, which contrasts with prior approaches involving chemical penetration enhancers and electromechanical devices.","journal":"Journal of Controlled Release","year":2025,"id":523652,"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":4,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9497,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":965202,"name":"Amy J. Wood‐Yang","orcid":"0000-0002-6219-8927","position":1,"is_corresponding":false},{"id":1396567,"name":"Nicholas Klavohn","orcid":null,"position":2,"is_corresponding":false},{"id":1396568,"name":"Nick Friesenhahn","orcid":null,"position":3,"is_corresponding":false},{"id":1396569,"name":"Nisha Raman","orcid":null,"position":4,"is_corresponding":false},{"id":1396065,"name":"Nusaiba Baker","orcid":"0000-0003-0737-2168","position":5,"is_corresponding":false},{"id":1053463,"name":"Grant Ashby","orcid":null,"position":6,"is_corresponding":false},{"id":231484,"name":"Mark R. Prausnitz","orcid":"0000-0002-9076-8448","position":7,"is_corresponding":false},{"id":1396566,"name":"Joshua I. Palacios","orcid":null,"position":0,"is_corresponding":true}],"reference_count":75,"raw_metadata":null,"created_at":"2026-07-19T02:50:03.004175Z","pmid":"40553757","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":[]}