{"doi":"10.3390/mps8060140","title":"A Rapid Fluorescence Method for In Vivo Quantitation of Lung Deposition of a Nebulized Drug: Multiple Uses for Advancing Aerosolized Drug Development and Specific Insight Regarding Aerosolized Vitamin A for Preventing Bronchopulmonary Dysplasia","abstract":"We have developed a method for in vivo quantitation of lung delivery of inhaled nebulized drugs by measuring a fluorescent-labeled analog in bronchioalveolar lavage fluid (BALF) collected immediately after inhalation dosing. The effectiveness of delivery of an aerosolized formulation of our proprietary water-miscible vitamin A product to the deep lung (target organ) was studied; the product is being developed for prevention of bronchopulmonary dysplasia (BPD) in preterm infants. The fluorescent retinol analog was incorporated by spiking into a standard formulation, remaining fully compatible with existing nebulizer administration procedures for animal exposure. The method provides quantitation of the delivered dose (DD) to the lung within a few minutes after dosing; fluorescence in BAL in a plate reader allows for simple rapid quantitation of the delivered drug, while avoiding the complexities of other labeling methods (e.g., heavy labels or radioactivity). Data from newborn rat and lamb models showed linear dose responses, validating the method. Approximately 5-10% of the inhaled drug was recovered in BALF in both models, consistent with reports in the literature. The ease of use of the method facilitated various aspects of our project, including the transition to more clinically relevant animal models and aerosol exposure systems. The formulation of this approach could be spiked into other formulations, allowing application of the method to other aerosol drug development programs.","journal":"Methods and Protocols","year":2025,"id":548548,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9547,"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":334208,"name":"Ying Wang","orcid":"0000-0003-0805-2991","position":1,"is_corresponding":false},{"id":1315021,"name":"Gourav Chandan","orcid":"0000-0001-6000-6605","position":2,"is_corresponding":false},{"id":1441746,"name":"Jie Liu","orcid":"0000-0002-2083-0883","position":3,"is_corresponding":false},{"id":1442256,"name":"S. Madrigal","orcid":null,"position":4,"is_corresponding":false},{"id":341000,"name":"Reiko Sakurai","orcid":null,"position":5,"is_corresponding":false},{"id":338386,"name":"C. Yu","orcid":null,"position":6,"is_corresponding":false},{"id":1287940,"name":"Catalina Guerra","orcid":"0000-0001-6381-7681","position":7,"is_corresponding":false},{"id":1441747,"name":"Robert Segal","orcid":"0000-0002-9621-0437","position":8,"is_corresponding":false},{"id":337039,"name":"Virender K. Rehan","orcid":"0000-0002-8948-8967","position":9,"is_corresponding":false},{"id":1441745,"name":"Craig A. Gelfand","orcid":"0009-0007-7349-7395","position":0,"is_corresponding":true}],"reference_count":21,"raw_metadata":null,"created_at":"2026-07-19T02:53:58.530220Z","pmid":"41283400","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":[]}