{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:46:09Z","timestamp":1791841569415,"version":"4.3.4"},"reference-count":36,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2026,12,1]],"date-time":"2026-12-01T00:00:00Z","timestamp":1796083200000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["19K16421"],"award-info":[{"award-number":["19K16421"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["26K09782"],"award-info":[{"award-number":["26K09782"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"published-print":{"date-parts":[[2026,12]]},"DOI":"10.1016\/j.ejpb.2026.115261","type":"journal-article","created":{"date-parts":[[2026,10,11]],"date-time":"2026-10-11T14:38:08Z","timestamp":1791729488000},"page":"115261","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":0,"special_numbering":"C","title":["Side-chain effects on solubility, chemical stability, and bioactivation of propofol ester prodrugs"],"prefix":"10.1016","volume":"229","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3233-6783","authenticated-orcid":false,"given":"Masato","family":"Takahashi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyoga","family":"Nishio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hikaru","family":"Yano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chanho","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuichiro","family":"Togashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5750-6369","authenticated-orcid":false,"given":"Masakiyo","family":"Hosokawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"key":"10.1016\/j.ejpb.2026.115261_b0005","doi-asserted-by":"crossref","first-page":"203","DOI":"10.2478\/cipms-2019-0035","article-title":"An overview of techniques for multifold enhancement in solubility of poorly soluble drugs","volume":"32","author":"Ansari","year":"2019","journal-title":"Curr. Issues Pharm. Med. Sci."},{"key":"10.1016\/j.ejpb.2026.115261_b0010","doi-asserted-by":"crossref","first-page":"110","DOI":"10.22270\/jddt.v13i2.5944","article-title":"Contemporary review on solubility enhancement techniques","volume":"13","author":"Narmada","year":"2023","journal-title":"J. Drug Deliv. Ther."},{"key":"10.1016\/j.ejpb.2026.115261_b0015","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.addr.2007.05.010","article-title":"Salt formation to improve drug solubility","volume":"59","author":"Serajuddin","year":"2007","journal-title":"Adv. Drug Deliv. Rev."},{"key":"10.1016\/j.ejpb.2026.115261_b0020","doi-asserted-by":"crossref","DOI":"10.1016\/j.ijpharm.2019.118498","article-title":"Is prodrug design an approach to increase water solubility?","volume":"568","author":"Sanches","year":"2019","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2026.115261_b0025","doi-asserted-by":"crossref","first-page":"2986","DOI":"10.1007\/s12325-019-01101-6","article-title":"Subcutaneous Injection of drugs: Literature Review of Factors Influencing Pain Sensation at the Injection Site","volume":"36","author":"Usach","year":"2019","journal-title":"Adv. Ther."},{"key":"10.1016\/j.ejpb.2026.115261_b0030","doi-asserted-by":"crossref","first-page":"975","DOI":"10.1111\/j.1365-2044.1990.tb14636.x","article-title":"pH\u2010adjustment and discomfort caused by the intradermal injection of lignocaine","volume":"45","author":"Martin","year":"1990","journal-title":"Anaesthesia"},{"key":"10.1016\/j.ejpb.2026.115261_b0035","first-page":"305","article-title":"Sterile Basics: Intravenous Admixture Preparation Considerations, Part 5: pH Considerations","volume":"24","author":"Allen","year":"2020","journal-title":"Int. J. Pharm. Compd."},{"key":"10.1016\/j.ejpb.2026.115261_b0040","doi-asserted-by":"crossref","first-page":"42","DOI":"10.3390\/molecules21010042","article-title":"The prodrug approach: a successful tool for improving drug solubility","volume":"21","author":"Jornada","year":"2015","journal-title":"Molecules"},{"key":"10.1016\/j.ejpb.2026.115261_b0045","doi-asserted-by":"crossref","first-page":"49","DOI":"10.54254\/3029-0821\/2025.21120","article-title":"Recent developments in phosphorus-containing ester prodrugs and its prospectives","volume":"3","author":"Huang","year":"2025","journal-title":"J. Food Sci. Nutr. Health"},{"key":"10.1016\/j.ejpb.2026.115261_b0050","doi-asserted-by":"crossref","DOI":"10.1155\/2018\/6852857","article-title":"Metabolic profiles of propofol and fospropofol: clinical and forensic interpretative aspects","volume":"2018","author":"Dinis-Oliveira","year":"2018","journal-title":"Biomed Res. Int."},{"key":"10.1016\/j.ejpb.2026.115261_b0055","first-page":"2318","article-title":"Amino acids in the development of prodrugs","volume":"23","author":"Vale","year":"2018","journal-title":"Mol. Basel Switz."},{"key":"10.1016\/j.ejpb.2026.115261_b0060","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1016\/S0928-0987(03)00161-1","article-title":"Highly water-soluble derivatives of the anesthetic agent propofol: in vitro and in vivo evaluation of cyclic amino acid esters","volume":"20","author":"Altomare","year":"2003","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2026.115261_b0065","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejpb.2025.114797","article-title":"Amino acid prodrug of capsaicin improves pharmacokinetic properties in the mouse brain and pancreas","volume":"214","author":"Tampio","year":"2025","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2026.115261_b0070","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.ejpb.2017.02.017","article-title":"New natural amino acid-bearing prodrugs boost pterostilbene\u2019s oral pharmacokinetic and distribution profile","volume":"115","author":"Azzolini","year":"2017","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2026.115261_b0075","doi-asserted-by":"crossref","first-page":"514","DOI":"10.1016\/j.ejpb.2013.12.009","article-title":"The development of orally administrable gemcitabine prodrugs with d-enantiomer amino acids: Enhanced membrane permeability and enzymatic stability","volume":"86","author":"Tsume","year":"2014","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2026.115261_b0080","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.ejpb.2015.01.001","article-title":"Rapid conversion of the ester prodrug abiraterone acetate results in intestinal supersaturation and enhanced absorption of abiraterone: In vitro, rat in situ and human in vivo studies","volume":"90","author":"Stappaerts","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2026.115261_b0085","doi-asserted-by":"crossref","first-page":"216","DOI":"10.1016\/j.ejpb.2014.12.014","article-title":"Lipophilic prodrugs of apomorphine I: Preparation, characterisation, and in vitro enzymatic hydrolysis in biorelevant media","volume":"89","author":"Borkar","year":"2015","journal-title":"Eur. J. Pharm. Biopharm."},{"key":"10.1016\/j.ejpb.2026.115261_b0090","doi-asserted-by":"crossref","first-page":"860","DOI":"10.1097\/00000542-200510000-00026","article-title":"Propofol: the challenges of Formulation","volume":"103","author":"Baker","year":"2005","journal-title":"Anesthesiology"},{"key":"10.1016\/j.ejpb.2026.115261_b0095","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1208\/s12249-007-9023-7","article-title":"Design and evaluation of microemulsions for improved parenteral delivery of propofol","volume":"9","author":"Date","year":"2008","journal-title":"AAPS PharmSciTech"},{"key":"10.1016\/j.ejpb.2026.115261_b0100","doi-asserted-by":"crossref","first-page":"79","DOI":"10.4103\/0970-9185.76656","article-title":"Fospropofol: clinical pharmacology","volume":"27","author":"Bengalorkar","year":"2011","journal-title":"J. Anaesthesiol. Clin. Pharmacol."},{"key":"10.1016\/j.ejpb.2026.115261_b0105","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1213\/ANE.0000000000000124","article-title":"An improved design of water-soluble propofol prodrugs characterized by rapid onset of action","volume":"118","author":"Lang","year":"2014","journal-title":"Anesth. Analg."},{"key":"10.1016\/j.ejpb.2026.115261_b0110","doi-asserted-by":"crossref","first-page":"7857","DOI":"10.1021\/acs.jmedchem.0c00698","article-title":"Design, synthesis, and activity study of water-soluble, rapid-release propofol prodrugs","volume":"63","author":"Liu","year":"2020","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejpb.2026.115261_b0115","doi-asserted-by":"crossref","first-page":"1813","DOI":"10.1016\/j.bmcl.2013.01.034","article-title":"Synthesis and characterization of novel quick-release propofol prodrug via lactonization","volume":"23","author":"Yang","year":"2013","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejpb.2026.115261_b0120","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.ejps.2018.09.024","article-title":"An improved water-soluble prodrug of propofol with high molecular utilization and rapid onset of action","volume":"127","author":"Zhang","year":"2019","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2026.115261_b0125","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1093\/bja\/aet218","article-title":"Efficacy comparison of the novel water-soluble propofol prodrug HX0969w and fospropofol in mice and rats","volume":"111","author":"Zhou","year":"2013","journal-title":"Br. J. Anaesth."},{"key":"10.1016\/j.ejpb.2026.115261_b0130","doi-asserted-by":"crossref","DOI":"10.1016\/j.bmcl.2024.129972","article-title":"Design, synthesis, and activity evaluation of water-soluble propofol derivatives as anesthetic drugs","volume":"113","author":"Huang","year":"2024","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"10.1016\/j.ejpb.2026.115261_b0135","unstructured":"Y. Zou, D. Chen, H. Chen, Y. Wang, X. Yuan, Alkaline amino acid ester salt of propofol, CN103880754A, 2014."},{"key":"10.1016\/j.ejpb.2026.115261_b0140","unstructured":"S.S. Hendler, Water-soluble prodrugs of propofol for treatment of migraine, WO2002013810 A1, 2002."},{"key":"10.1016\/j.ejpb.2026.115261_b0145","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.ijpharm.2004.02.028","article-title":"Evaluation of new propofol aqueous solutions for intravenous anesthesia","volume":"278","author":"Trapani","year":"2004","journal-title":"Int. J. Pharm."},{"key":"10.1016\/j.ejpb.2026.115261_b0150","doi-asserted-by":"crossref","first-page":"79","DOI":"10.5114\/ait.2021.103542","article-title":"Systematic review of the stability and compatibility of propofol injection","volume":"53","author":"Husna","year":"2021","journal-title":"Anaesthesiol. Intensive Ther."},{"key":"10.1016\/j.ejpb.2026.115261_b0155","doi-asserted-by":"crossref","DOI":"10.1016\/j.ejps.2020.105455","article-title":"Design, synthesis and biological evaluation of water-soluble phenytoin prodrugs considering the substrate recognition ability of human carboxylesterase 1","volume":"152","author":"Takahashi","year":"2020","journal-title":"Eur. J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2026.115261_b0160","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1002\/wcms.1261","article-title":"The Baldwin rules: revised and extended","volume":"6","author":"Gilmore","year":"2016","journal-title":"WIREs Comput. Mol. Sci."},{"key":"10.1016\/j.ejpb.2026.115261_b0165","doi-asserted-by":"crossref","DOI":"10.1016\/j.dmpk.2021.100391","article-title":"Effects of steric hindrance and electron density of ester prodrugs on controlling the metabolic activation by human carboxylesterase","volume":"38","author":"Takahashi","year":"2021","journal-title":"Drug Metab. Pharmacokinet."},{"key":"10.1016\/j.ejpb.2026.115261_b0170","doi-asserted-by":"crossref","DOI":"10.1016\/j.xphs.2025.104146","article-title":"Design and synthesis of carbamate-linked ester prodrugs selectively activated by carboxylesterase 1 with enhanced stability against intestinal hydrolysis","volume":"115","author":"Takahashi","year":"2026","journal-title":"J. Pharm. Sci."},{"key":"10.1016\/j.ejpb.2026.115261_b0175","doi-asserted-by":"crossref","DOI":"10.1016\/j.bcp.2023.115910","article-title":"Drug and pro-drug substrates and pseudo-substrates of human butyrylcholinesterase","volume":"218","author":"Masson","year":"2023","journal-title":"Biochem. Pharmacol."},{"key":"10.1016\/j.ejpb.2026.115261_b0180","doi-asserted-by":"crossref","first-page":"5453","DOI":"10.2147\/DDDT.S516789","article-title":"Clinical use of Fospropofol Disodium: Evaluation of Pharmacology, Safety, and Efficacy","volume":"19","author":"Zou","year":"2025","journal-title":"Drug Des. Devel. Ther."}],"container-title":["European Journal of Pharmaceutics and Biopharmaceutics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641126002821?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0939641126002821?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T21:03:46Z","timestamp":1791839026000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0939641126002821"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,12]]},"references-count":36,"alternative-id":["S0939641126002821"],"URL":"https:\/\/doi.org\/10.1016\/j.ejpb.2026.115261","relation":{},"ISSN":["0939-6411"],"issn-type":[{"value":"0939-6411","type":"print"}],"subject":[],"published":{"date-parts":[[2026,12]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Side-chain effects on solubility, chemical stability, and bioactivation of propofol ester prodrugs","name":"articletitle","label":"Article Title"},{"value":"European Journal of Pharmaceutics and Biopharmaceutics","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejpb.2026.115261","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2026 Elsevier B.V. All rights are reserved, including those for text and data mining, AI training, and similar technologies.","name":"copyright","label":"Copyright"}],"article-number":"115261"}}