{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T02:52:39Z","timestamp":1785552759542,"version":"3.56.0"},"reference-count":23,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,2,18]],"date-time":"2019-02-18T00:00:00Z","timestamp":1550448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Dantrolene sodium (DS) is the only drug specifically used for the treatment of malignant hyperthermia. Nevertheless, its clinical application is significantly restricted due to its aqueous insolubility and the limited formulations available in clinical practice. In order to solve these problems, a novel mixed micelle composed of phospholipid and Cremophor EL was designed and evaluated. The mixed micelle was prepared using a stirring- ultrasonic method. The Dynamic Light Scattering (DLS) results showed that the micelle was small in size (12.14 nm) and narrowly distributed (PdI = 0.073). Transmission Electron Microscopy (TEM) images showed that the micelle was homogeneous and spherical. The stability study indicated that the system was stable for storage and dilution with distilled water, while the safety testing showed that the micelle was safe for intravenous administration with low hemolysis rates and low allergic reaction rates. In the pharmaceutics study, the Cmax and AUC0-t of the DS-loaded micelle were 4- and 4.5- folds higher than that of the DS. Therefore, the constructed phospholipid-Cremophor EL mixed micelle is a promising drug delivery system for DS.<\/jats:p>","DOI":"10.3390\/molecules24040728","type":"journal-article","created":{"date-parts":[[2019,2,19]],"date-time":"2019-02-19T04:08:20Z","timestamp":1550549300000},"page":"728","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["A Novel Dantrolene Sodium-Loaded Mixed Micelle Containing a Small Amount of Cremophor EL: Characterization, Stability, Safety and Pharmacokinetics"],"prefix":"10.3390","volume":"24","author":[{"given":"Wenzhen","family":"Jin","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochuan","family":"Tan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin","family":"Wen","sequence":"additional","affiliation":[{"name":"Chinese Pharmaceutical Association, Beijing 100022, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ya","family":"Meng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujia","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He","family":"Li","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Jiang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hui","family":"Song","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wensheng","family":"Zheng","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Bioactive Substance and Function of Natural Medicines &amp; Beijing Key laboratory of Drug Delivery Technology and Novel Formulation, Institute of Materia Medica, Chinese Academy of Medical Sciences &amp; Peking Union Medical College, Beijing 100050, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,2,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2918","DOI":"10.1001\/jama.293.23.2918","article-title":"Malignant hyperthermia: Update on susceptibility testing","volume":"293","author":"Litman","year":"2005","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1093\/bja\/34.6.395","article-title":"Anaesthetic deaths in a family","volume":"34","author":"Denborough","year":"1962","journal-title":"Br. J. Anaesth."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1186\/s13023-015-0310-1","article-title":"Malignant hyperthermia: A review","volume":"10","author":"Rosenberg","year":"2015","journal-title":"Orphanet. J. Rare Dis."},{"key":"ref_4","first-page":"700","article-title":"Incidence of malignant hyperthermia in Denmark","volume":"64","author":"Ording","year":"1985","journal-title":"Anesth. Analg."},{"key":"ref_5","first-page":"203","article-title":"Pharmacokinetics of intravenously administered dantrolene and its 5-hydroxy metabolite in dogs","volume":"10","author":"Wuis","year":"1990","journal-title":"Int. J. Clin. Pharmacol. Res."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"632","DOI":"10.1097\/00003643-200110000-00002","article-title":"Malignant hyperthermia","volume":"18","author":"Wappler","year":"2001","journal-title":"Eur. J. Anaesthesiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1016\/0378-5173(91)90193-R","article-title":"Some physical-chemical properties of dantrolene and two of its analogues","volume":"75","author":"Jansen","year":"1991","journal-title":"Int. J. Pha."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"597","DOI":"10.3109\/03639045.2010.533276","article-title":"Phospholipid\u2013Tween 80 mixed micelles as an intravenous delivery carrier for paclitaxel","volume":"37","author":"Liang","year":"2011","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"2279","DOI":"10.1248\/bpb.30.2279","article-title":"The Effect of Survivin on Multidrug Resistance Mediated by P-Glycoprotein in MCF-7 and Its Adriamycin Resistant Cells","volume":"30","author":"Liu","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.jconrel.2004.09.021","article-title":"Controlled and targeted tumor chemotherapy by micellar-encapsulated drug and ultrasound","volume":"102","author":"Gao","year":"2005","journal-title":"J. Control. Release."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/j.ejps.2005.07.002","article-title":"Permeabilization and solubilization of soybean phosphatidylcholine bilayer vesicles, as membrane models, by polysorbate, Tween 80","volume":"26","author":"Tapadas","year":"2005","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"269","DOI":"10.1016\/0304-4157(95)00010-O","article-title":"Interaction of detergents with lipid vesicles","volume":"1241","author":"Lasch","year":"1995","journal-title":"Biochim. Biophys. Acta."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0378-4347(98)00043-7","article-title":"Influence of Cremophor EL on the quantification of paclitaxel in plasma using high-performance liquid chromatography with solid-phase extraction as sample pretreatment","volume":"709","author":"Huizing","year":"1998","journal-title":"J. Chromatogr. B Biomed. Sci. Appl."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.3109\/03639045.2010.487263","article-title":"Application of rotatable central composite design in the preparation and optimization of poly(lactic-co-glycolic acid) nanoparticles for controlled delivery of paclitaxel","volume":"36","author":"Sivacharan","year":"2010","journal-title":"Drug Dev. Ind. Pharm."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1273","DOI":"10.1016\/j.addr.2003.12.004","article-title":"Micelles from lipid derivatives of water-soluble polymers as delivery systems for poorly soluble drugs","volume":"56","author":"Lukyanov","year":"2004","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.pharma.2017.06.003","article-title":"Extended stability of the rituximab biosimilar CT-P10 in its opened vials and after dilution and storage in polyolefin bags","volume":"75","author":"Vieillard","year":"2017","journal-title":"Ann. Pharm. Fr."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1016\/j.jcis.2007.09.053","article-title":"Preparation and properties of mixed micelles made of Pluronic polymer and PEG-PE","volume":"317","author":"Li","year":"2008","journal-title":"J. Colloid. Interface Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.biomaterials.2006.09.035","article-title":"Shell-crosslinked Pluronic L121 micelles as a drug delivery vehicle","volume":"28","author":"Yang","year":"2007","journal-title":"Biomaterials"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ejps.2003.11.009","article-title":"Development of a dissolution medium for nimodipine tablets based on bioavailability evaluation","volume":"21","author":"He","year":"2004","journal-title":"Eur. J. Pharm. Sci."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.colsurfb.2017.03.056","article-title":"Precise ratiometric loading of PTX and DOX based on redox-sensitive mixed micelles for cancer therapy","volume":"155","author":"Zhao","year":"2017","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"208","DOI":"10.1248\/bpb.b14-00508","article-title":"Enhanced Oral Bioavailability of Morin Administered in Mixed Micelle Formulation with PluronicF127 and Tween80 in Rats","volume":"38","author":"Choi","year":"2015","journal-title":"Biol. Pharm. Bull."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"9388","DOI":"10.1021\/la048354h","article-title":"Physicochemical characterization of degradable thermosensitive polymeric micelles","volume":"20","author":"Soga","year":"2004","journal-title":"Langmuir"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"6633","DOI":"10.1016\/j.biomaterials.2011.05.050","article-title":"Well-defined, Reversible Disulfide Cross-linked Micelles for On-demand Paclitaxel Delivery","volume":"32","author":"Li","year":"2011","journal-title":"Biomaterials"}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/4\/728\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:32:49Z","timestamp":1760185969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/24\/4\/728"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,2,18]]},"references-count":23,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,2]]}},"alternative-id":["molecules24040728"],"URL":"https:\/\/doi.org\/10.3390\/molecules24040728","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,2,18]]}}}