{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T19:15:32Z","timestamp":1790709332630,"version":"4.1.0"},"reference-count":43,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T00:00:00Z","timestamp":1739232000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"publisher","award":["7749108"],"award-info":[{"award-number":["7749108"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"publisher","award":["451-03-65\/2024-03\/200161"],"award-info":[{"award-number":["451-03-65\/2024-03\/200161"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"publisher","award":["451-03-66\/2024-03\/200161"],"award-info":[{"award-number":["451-03-66\/2024-03\/200161"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"publisher","award":["451-03-66\/2024-03\/200026"],"award-info":[{"award-number":["451-03-66\/2024-03\/200026"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100016047","name":"Science Fund of the Republic of Serbia","doi-asserted-by":"publisher","award":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"],"award-info":[{"award-number":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"]}],"id":[{"id":"10.13039\/501100016047","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ministry of Education, Science and Technological Development, Republic of Serbia","award":["7749108"],"award-info":[{"award-number":["7749108"]}]},{"name":"Ministry of Education, Science and Technological Development, Republic of Serbia","award":["451-03-65\/2024-03\/200161"],"award-info":[{"award-number":["451-03-65\/2024-03\/200161"]}]},{"name":"Ministry of Education, Science and Technological Development, Republic of Serbia","award":["451-03-66\/2024-03\/200161"],"award-info":[{"award-number":["451-03-66\/2024-03\/200161"]}]},{"name":"Ministry of Education, Science and Technological Development, Republic of Serbia","award":["451-03-66\/2024-03\/200026"],"award-info":[{"award-number":["451-03-66\/2024-03\/200026"]}]},{"name":"Ministry of Education, Science and Technological Development, Republic of Serbia","award":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"],"award-info":[{"award-number":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"]}]},{"name":"University of Belgrade","award":["7749108"],"award-info":[{"award-number":["7749108"]}]},{"name":"University of Belgrade","award":["451-03-65\/2024-03\/200161"],"award-info":[{"award-number":["451-03-65\/2024-03\/200161"]}]},{"name":"University of Belgrade","award":["451-03-66\/2024-03\/200161"],"award-info":[{"award-number":["451-03-66\/2024-03\/200161"]}]},{"name":"University of Belgrade","award":["451-03-66\/2024-03\/200026"],"award-info":[{"award-number":["451-03-66\/2024-03\/200026"]}]},{"name":"University of Belgrade","award":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"],"award-info":[{"award-number":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"]}]},{"name":"Faculty of Pharmacy","award":["7749108"],"award-info":[{"award-number":["7749108"]}]},{"name":"Faculty of Pharmacy","award":["451-03-65\/2024-03\/200161"],"award-info":[{"award-number":["451-03-65\/2024-03\/200161"]}]},{"name":"Faculty of Pharmacy","award":["451-03-66\/2024-03\/200161"],"award-info":[{"award-number":["451-03-66\/2024-03\/200161"]}]},{"name":"Faculty of Pharmacy","award":["451-03-66\/2024-03\/200026"],"award-info":[{"award-number":["451-03-66\/2024-03\/200026"]}]},{"name":"Faculty of Pharmacy","award":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"],"award-info":[{"award-number":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"]}]},{"name":"Institute of Chemistry, Technology and Metallurgy","award":["7749108"],"award-info":[{"award-number":["7749108"]}]},{"name":"Institute of Chemistry, Technology and Metallurgy","award":["451-03-65\/2024-03\/200161"],"award-info":[{"award-number":["451-03-65\/2024-03\/200161"]}]},{"name":"Institute of Chemistry, Technology and Metallurgy","award":["451-03-66\/2024-03\/200161"],"award-info":[{"award-number":["451-03-66\/2024-03\/200161"]}]},{"name":"Institute of Chemistry, Technology and Metallurgy","award":["451-03-66\/2024-03\/200026"],"award-info":[{"award-number":["451-03-66\/2024-03\/200026"]}]},{"name":"Institute of Chemistry, Technology and Metallurgy","award":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"],"award-info":[{"award-number":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"]}]},{"name":"National Institutes of Health, USA","award":["7749108"],"award-info":[{"award-number":["7749108"]}]},{"name":"National Institutes of Health, USA","award":["451-03-65\/2024-03\/200161"],"award-info":[{"award-number":["451-03-65\/2024-03\/200161"]}]},{"name":"National Institutes of Health, USA","award":["451-03-66\/2024-03\/200161"],"award-info":[{"award-number":["451-03-66\/2024-03\/200161"]}]},{"name":"National Institutes of Health, USA","award":["451-03-66\/2024-03\/200026"],"award-info":[{"award-number":["451-03-66\/2024-03\/200026"]}]},{"name":"National Institutes of Health, USA","award":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"],"award-info":[{"award-number":["2R01 DA043204-06A1 (NIDA), R01 AA029023 (NIAAA) and R01 DA054177 (NIDA)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Background\/Objectives: The novel pyrazoloquinolinone ligand CW-02-79 shows a unique profile of selective binding to \u03c32 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\u2013brain 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\u2014phospholipid 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 \u00b0C. 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 \u03c32 receptors.<\/jats:p>","DOI":"10.3390\/pharmaceutics17020232","type":"journal-article","created":{"date-parts":[[2025,2,11]],"date-time":"2025-02-11T09:36:05Z","timestamp":1739266565000},"page":"232","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Intravenous Nanoemulsions Loaded with Phospholipid Complex of a Novel Pyrazoloquinolinone Ligand for Enhanced Brain Delivery"],"prefix":"10.3390","volume":"17","author":[{"given":"Tijana","family":"Stankovi\u0107","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tanja","family":"Ili\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Branka","family":"Divovi\u0107 Matovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9637-1380","authenticated-orcid":false,"given":"Milos","family":"Petkovic","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5086-9017","authenticated-orcid":false,"given":"Vladimir","family":"Dobri\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ivan","family":"Jan\u010di\u0107","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Biljana","family":"Bufan","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Immunology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kristina","family":"Jezdi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0936-4276","authenticated-orcid":false,"given":"Jelena","family":"\u0110okovi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6164-4457","authenticated-orcid":false,"given":"Ivana","family":"Panteli\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0780-5058","authenticated-orcid":false,"given":"Danijela","family":"Randjelovi\u0107","sequence":"additional","affiliation":[{"name":"Institute of Chemistry, Technology and Metallurgy, National Institute of the Republic of Serbia, University of Belgrade, 11000 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dishary","family":"Sharmin","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5512-3022","authenticated-orcid":false,"given":"James M.","family":"Cook","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry, Milwaukee Institute for Drug Discovery, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miroslav M.","family":"Savi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6236-9730","authenticated-orcid":false,"given":"Sne\u017eana","family":"Savi\u0107","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Technology and Cosmetology, Faculty of Pharmacy, University of Belgrade, 11211 Belgrade, Serbia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/0024-3205(82)90573-2","article-title":"CGS 8216: Receptor binding characteristics of a potent benzodiazepine antagonist","volume":"30","author":"Czernik","year":"1982","journal-title":"Life Sci."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"2422","DOI":"10.1021\/acs.jmedchem.7b01664","article-title":"Design and Synthesis of Novel Deuterated Ligands Functionally Selective for the \u03b3-Aminobutyric Acid Type A Receptor (GABAAR) \u03b16 Subtype with Improved Metabolic Stability and Enhanced Bioavailability","volume":"61","author":"Knutson","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1038\/s41419-024-06693-8","article-title":"Cytotoxic sigma-2 ligands trigger cancer cell death via cholesterol-induced-ER-stress","volume":"15","author":"Takchi","year":"2024","journal-title":"Cell Death Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1582","DOI":"10.1007\/s43440-021-00310-7","article-title":"Sigma receptors and neurological disorders","volume":"73","author":"Piechal","year":"2021","journal-title":"Pharmacol. Rep."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1007\/s40263-023-01007-6","article-title":"Targeting Sigma Receptors for the Treatment of Neurodegenerative and Neurodevelopmental Disorders","volume":"37","author":"Malar","year":"2023","journal-title":"CNS Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1208\/s12249-018-1252-4","article-title":"Drug-Phospholipid Complex-a Go Through Strategy for Enhanced Oral Bioavailability","volume":"20","author":"Kuche","year":"2019","journal-title":"AAPS PharmSciTech"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1016\/j.jconrel.2022.07.014","article-title":"Tailoring the multi-functional properties of phospholipids for simple to complex self-assemblies","volume":"349","author":"Waghule","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1208\/s12249-024-02813-x","article-title":"Phospholipid Complex Formulation Technology for Improved Drug Delivery in Oncological Settings: A Comprehensive Review","volume":"25","author":"Patil","year":"2024","journal-title":"AAPS PharmSciTech"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2699","DOI":"10.1021\/acs.molpharmaceut.3c00983","article-title":"Gemcitabine-Phospholipid Complex Loaded Lipid Nanoparticles for Improving Drug Loading, Stability, and Efficacy against Pancreatic Cancer","volume":"21","author":"Dora","year":"2024","journal-title":"Mol. Pharm."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"5629","DOI":"10.2147\/IJN.S261162","article-title":"Self-Assembled Lecithin\/Chitosan Nanoparticles Based on Phospholipid Complex: A Feasible Strategy to Improve Entrapment Efficiency and Transdermal Delivery of Poorly Lipophilic Drug","volume":"15","author":"Dong","year":"2020","journal-title":"Int. J. Nanomed."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"306","DOI":"10.1016\/j.ijpharm.2014.01.023","article-title":"Solid dispersion of berberine-phospholipid complex\/TPGS 1000\/SiO2: Preparation, characterization and in vivo studies","volume":"465","author":"Zhang","year":"2014","journal-title":"Int. J. Pharm."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1016\/j.ijpharm.2008.09.008","article-title":"Formulation of an intravenous emulsion loaded with a clarithromycin-phospholipid complex and its pharmacokinetics in rats","volume":"366","author":"Lu","year":"2009","journal-title":"Int. J. Pharm."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1016\/j.ijpharm.2013.06.032","article-title":"Development of intravenous lipid emulsion of vinorelbine based on drug-phospholipid complex technique","volume":"454","author":"Li","year":"2013","journal-title":"Int. J. Pharm."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2183834","DOI":"10.1080\/10717544.2023.2183834","article-title":"Preparation and in vivo evaluation of an intravenous emulsion loaded with an aprepitant-phospholipid complex","volume":"30","author":"Li","year":"2023","journal-title":"Drug Deliv."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"119098","DOI":"10.1016\/j.ijpharm.2020.119098","article-title":"Nanopharmaceuticals: A focus on their clinical translatability","volume":"578","author":"Bisso","year":"2020","journal-title":"Int. J. Pharm."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ili\u0107, T., \u0110okovi\u0107, J.B., Nikoli\u0107, I., Mitrovi\u0107, J.R., Panteli\u0107, I., Savi\u0107, S.D., and Savi\u0107, M.M. (2023). Parenteral Lipid-Based Nanoparticles for CNS Disorders: Integrating Various Facets of Preclinical Evaluation towards More Effective Clinical Translation. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15020443"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gajbhiye, K.R., Pawar, A., Mahadik, K.R., and Gajbhiye, V. (2020). PEGylated nanocarriers: A promising tool for targeted delivery to the brain. Colloids Surf. B Biointerfaces, 187.","DOI":"10.1016\/j.colsurfb.2019.110770"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"124888","DOI":"10.1016\/j.molliq.2024.124888","article-title":"Evaluation of PEGylation efficacy of curcumin-loaded nanoemulsions using complementary methods to assess protein interactions and physicochemical properties","volume":"404","author":"Demisli","year":"2024","journal-title":"J. Mol. Liq."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1620","DOI":"10.1021\/acschemneuro.0c00076","article-title":"GLUT-1: An Effective Target to Deliver Brain-Derived Neurotrophic Factor Gene Across the Blood Brain Barrier","volume":"11","author":"Arora","year":"2020","journal-title":"ACS Chem. Neurosci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/j.jconrel.2014.03.006","article-title":"The role of glucose transporters in the distribution of p-aminophenyl-\u03b1-d-mannopyranoside modified liposomes within mice brain","volume":"182","author":"Du","year":"2014","journal-title":"J. Control. Release"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3234","DOI":"10.1021\/acsnano.3c09715","article-title":"Mannose-Integrated Nanoparticle Hitchhike Glucose Transporter 1 Recycling to Overcome Various Barriers of Oral Delivery for Alzheimer\u2019s Disease Therapy","volume":"18","author":"Lei","year":"2024","journal-title":"ACS Nano"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"4168","DOI":"10.1021\/acs.molpharmaceut.6b00773","article-title":"Pulmonary Surfactant Protein A-Mediated Enrichment of Surface-Decorated Polymeric Nanoparticles in Alveolar Macrophages","volume":"13","author":"Ruge","year":"2016","journal-title":"Mol. Pharm."},{"key":"ref_23","first-page":"694","article-title":"Targeted delivery of chlorogenic acid by mannosylated liposomes to effectively promote the polarization of TAMs for the treatment of glioblastoma","volume":"5","author":"Ye","year":"2020","journal-title":"Bioact. Mater."},{"key":"ref_24","unstructured":"(2024, December 27). iCell Blood-Brain Barrier Isogenic Kit. Available online: https:\/\/www.fujifilmcdi.com\/icell-blood-brain-barrier-isogenic-kit-01279-r1241."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.ejpb.2018.03.007","article-title":"Mimicking brain tissue binding in an in vitro model of the blood-brain barrier illustrates differences between in vitro and in vivo methods for assessing the rate of brain penetration","volume":"127","author":"Heymans","year":"2018","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Rantanen, J., Rades, T., and Strachan, C. (2023). Solid-state analysis for pharmaceuticals: Pathways to feasible and meaningful analysis. J. Pharm. Biomed. Anal., 236.","DOI":"10.1016\/j.jpba.2023.115649"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.ijpharm.2017.10.053","article-title":"Self-assembled phospholipid-based phytosomal nanocarriers as promising platforms for improving oral bioavailability of the anticancer celastrol","volume":"535","author":"Freag","year":"2018","journal-title":"Int. J. Pharm."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.1007\/s13346-020-00833-1","article-title":"Novel rhein-phospholipid complex targeting skin diseases: Development, in vitro, ex vivo, and in vivo studies","volume":"11","author":"Ebada","year":"2021","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1007\/s13346-018-0497-5","article-title":"Local sustained delivery of bupivacaine HCl from a new castor oil-based nanoemulsion system","volume":"8","author":"Rachmawati","year":"2018","journal-title":"Drug Deliv. Transl. Res."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Pires, P.C., Paiva-Santos, A.C., and Veiga, F. (2022). Antipsychotics-Loaded Nanometric Emulsions for Brain Delivery. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102174"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.ijpharm.2015.07.007","article-title":"Parenteral nanoemulsions as promising carriers for brain delivery of risperidone: Design, characterization and in vivo pharmacokinetic evaluation","volume":"493","author":"Daniels","year":"2015","journal-title":"Int. J. Pharm."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"722","DOI":"10.1016\/j.jconrel.2020.09.043","article-title":"Lactose-appended \u03b2-cyclodextrin as an effective nanocarrier for brain delivery","volume":"328","author":"Yokoyama","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1007\/s11095-016-1867-7","article-title":"Multimodal Dispersion of Nanoparticles: A Comprehensive Evaluation of Size Distribution with 9 Size Measurement Methods","volume":"33","author":"Varenne","year":"2016","journal-title":"Pharm. Res."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jconrel.2022.05.055","article-title":"Artificial engineering of the protein corona at bio-nano interfaces for improved cancer-targeted nanotherapy","volume":"348","author":"Khan","year":"2022","journal-title":"J. Control. Release"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"28559","DOI":"10.1021\/acsami.2c05362","article-title":"Nanoparticle-Protein Interaction: Demystifying the Correlation between Protein Corona and Aggregation Phenomena","volume":"14","author":"Ferreira","year":"2022","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.jconrel.2009.10.005","article-title":"Impact of emulsion-based drug delivery systems on intestinal permeability and drug release kinetics","volume":"142","author":"Buyukozturk","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0928-0987(01)00095-1","article-title":"Modeling and comparison of dissolution profiles","volume":"13","author":"Costa","year":"2001","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Zhu, Q., Huang, Y., Zhu, X., Peng, L., Wang, H., Gao, S., Yang, Z., Zhang, J., and Liu, X. (2023). Mannose-coated superparamagnetic iron oxide nanozyme for preventing postoperative cognitive dysfunction. Mater. Today Bio, 19.","DOI":"10.1016\/j.mtbio.2023.100568"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"20410","DOI":"10.1021\/acsami.7b03504","article-title":"In Vitro Study of Receptor-Mediated Silica Nanoparticles Delivery across Blood-Brain Barrier","volume":"9","author":"Song","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Handa, M., Sanap, S.N., Bhatta, R.S., Patil, G.P., Ghose, S., Singh, D.P., and Shukla, R. (2023). Combining donepezil and memantine via mannosylated PLGA nanoparticles for intranasal delivery: Characterization and preclinical studies. Biomater. Adv., 154.","DOI":"10.1016\/j.bioadv.2023.213663"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1021\/jm501535r","article-title":"CNS drug design: Balancing physicochemical properties for optimal brain exposure","volume":"58","author":"Rankovic","year":"2015","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1321","DOI":"10.1007\/s11095-022-03246-6","article-title":"Unbound Brain-to-Plasma Partition Coefficient, Kp,uu,brain\u2014A Game Changing Parameter for CNS Drug Discovery and Development","volume":"39","author":"Loryan","year":"2022","journal-title":"Pharm. Res."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Li, J., F\u00e9lix-Soriano, E., Wright, K.R., Shen, H., Baer, L.A., Stanford, K.I., and Guo, L.W. (2022). Differential Responses to Sigma-1 or Sigma-2 Receptor Ablation in Adiposity, Fat Oxidation, and Sexual Dimorphism. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms231810846"}],"container-title":["Pharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/2\/232\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:30:55Z","timestamp":1760027455000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4923\/17\/2\/232"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,11]]},"references-count":43,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2025,2]]}},"alternative-id":["pharmaceutics17020232"],"URL":"https:\/\/doi.org\/10.3390\/pharmaceutics17020232","relation":{},"ISSN":["1999-4923"],"issn-type":[{"value":"1999-4923","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,11]]}}}