{"doi":"10.3390/pharmaceutics17020232","title":"Intravenous Nanoemulsions Loaded with Phospholipid Complex of a Novel Pyrazoloquinolinone Ligand for Enhanced Brain Delivery","abstract":"Background/Objectives: The novel pyrazoloquinolinone ligand CW-02-79 shows a unique profile of selective binding to σ2 receptors, but its poor solubility in both water and lipids makes its research and development a burdensome task. We aimed to develop a phospholipid-complex-based nanoemulsion formulation containing CW-02-79 suitable for intravenous administration in preclinical research. Methods: The decorated and undecorated nanoemulsions were formulated and subjected to detailed physiochemical characterization. The delivery and exposure to CW-02-79 from selected nanoemulsions were examined in the in vitro blood–brain barrier model based on human-induced pluripotent stem-cell-derived microvascular endothelial cells, astrocytes, and pericytes, and in vivo neuropharmacokinetic study in rats, respectively. Results: The developed biocompatible nanoemulsions loaded with a CW-02-79—phospholipid complex at a mass ratio of 1:10 exhibited a small droplet size and narrow size distribution, with satisfactory physicochemical stability during steam sterilization and short-term storage at 25 °C. The analysis of protein binding interactions revealed that the PEGylated nanoemulsions had fewer observable interactions compared to the undecorated nanoemulsions, especially when 0.2% DSPE-PEG2000 and 0.1% DSPE-PEG2000-mannose were combined. An in vitro BBB study demonstrated that a substantial part of CW-02-79 present in the applied nanoemulsion is able to permeate the barrier. The quantification of CW-02-79 in plasma/brain homogenate and calculated pharmacokinetic parameters confirmed good systemic and brain availability after intravenous administration. There were subtle differences in the pharmacokinetic parameters in favor of a dual surface-functionalized nanoemulson containing the glucose transporter-1-targeting ligand (mannose). Conclusions: The developed and characterized nanoemulsions enable substantial brain exposure to CW-02-79 as a prerequisite for a pharmacologically and clinically relevant selective modulation of σ2 receptors.","journal":"Pharmaceutics","year":2025,"id":522708,"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":0.9551,"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":1387517,"name":"Jela Milić","orcid":"0000-0002-1937-1704","position":1,"is_corresponding":false},{"id":454637,"name":"Branka Divović","orcid":"0000-0002-5037-1382","position":2,"is_corresponding":false},{"id":1394832,"name":"Miloš Petković","orcid":"0000-0001-9637-1380","position":3,"is_corresponding":false},{"id":454642,"name":"Vladimir Dobričić","orcid":"0000-0002-5086-9017","position":4,"is_corresponding":false},{"id":1387516,"name":"Ivan Jančić","orcid":"0000-0002-8481-9536","position":5,"is_corresponding":false},{"id":1387518,"name":"Biljana Bufan","orcid":"0000-0003-1861-5700","position":6,"is_corresponding":false},{"id":1387515,"name":"Kristina Jezdić","orcid":"0009-0000-2208-2252","position":7,"is_corresponding":false},{"id":454639,"name":"Jelena Đoković","orcid":"0000-0003-0936-4276","position":8,"is_corresponding":false},{"id":760969,"name":"Ivana Pantelić","orcid":"0000-0001-6164-4457","position":9,"is_corresponding":false},{"id":454641,"name":"Danijela Randjelović","orcid":"0000-0003-0780-5058","position":10,"is_corresponding":false},{"id":524992,"name":"Dishary Sharmin","orcid":"0000-0003-0417-4262","position":11,"is_corresponding":false},{"id":445008,"name":"James M. Cook","orcid":"0000-0001-5512-3022","position":12,"is_corresponding":false},{"id":454644,"name":"Miroslav M. Savić","orcid":"0000-0002-6934-9193","position":13,"is_corresponding":false},{"id":454645,"name":"Snežana Savić","orcid":"0000-0002-6236-9730","position":14,"is_corresponding":false},{"id":1387521,"name":"Tijana Stanković","orcid":"0000-0001-5623-0612","position":0,"is_corresponding":true}],"reference_count":43,"raw_metadata":null,"created_at":"2026-07-19T02:49:58.707747Z","pmid":"40006599","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":[]}