{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T06:05:09Z","timestamp":1785391509027,"version":"3.55.0"},"reference-count":32,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T00:00:00Z","timestamp":1675382400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"King Fahad Medical City, research center, Kingdom of Saudi Arabia","award":["19-564"],"award-info":[{"award-number":["19-564"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Purpose: Propofol is a relatively short-acting potent anesthetic lipophilic drug used during short surgical procedures. Despite the success of propofol intravenous emulsions, drawbacks to such formulations include inherent emulsion instability, the lack of a safe vehicle to prevent sepsis, and concern regarding hyperlipidemia-related side effects. The aim of the current investigation was to develop a novel, lipid-based self-nanoemulsifying drug delivery system (SNEDDS) for propofol with improved stability and anesthetic activity for human use. Methods: A series of SNEDDS formulations were developed using naturally obtained medium-chain\/long-chain mono-, di-, and triglycerides, glyceryl monocaprylate, and water-soluble cosolvents with hydrogenated castor oil constructing ternary phase diagrams for propofol. The developed SNEDDS formulations were characterized using visual observation, particle size analysis, zeta potential, transmission electron microscopy, equilibrium solubility, in vitro dynamic dispersion and stability, and in vivo sleeping disorder studies in rats. The in vivo bioavailability of the SNEDDSs in rats was also studied to compare the representative formulations with the marketed product Diprivan\u00ae. Results: Medium-chain triglycerides (M810) with mono-diglycerides (CMCM) as an oil blend and hydrogenated castor oil (KHS15) as a surfactant were selected as key ingredients in ternary phase diagram studies. The nanoemulsifying regions were identified from the studies and a number of SNEDDSs were formulated. Results from the characterization studies demonstrated the formation of efficient nanosized particles (28\u201345 nm globule size, 0.10\u20130.20 PDI) in the optimized SNEDDS with a drug loading of 50 mg\/g, which is almost 500-fold higher than free propofol. TEM analysis showed the formation of spherical and homogeneous nanoparticles of less than 50 nm. The dissolution rate of the representative SNEDDS was faster than raw propofol and able to maintain 99% propofol in aqueous solution for around 24 h. The optimized liquid SNEDDS formulation was found to be thermodynamically stable. The intravenous administration of the SNEDDS in male Wistar rats induced a sleeping time of 73\u201388 min. The mean plasma concentrations after the IV administration of propofol nano-formulations PF2-SNEDDS and PF8-SNEDDS were 1348.07 \u00b1 27.31 and 1138.66 \u00b1 44.97 \u00b5g\/mL, as compared to 891.44 \u00b1 26.05 \u00b5g\/mL (p = 0.05) observed after the IV administration of raw propofol. Conclusion: Propofol-loaded SNEDDS formulations could be a potential pharmaceutical product with improved stability, bioavailability, and anesthetic activity.<\/jats:p>","DOI":"10.3390\/molecules28031492","type":"journal-article","created":{"date-parts":[[2023,2,3]],"date-time":"2023-02-03T05:31:24Z","timestamp":1675402284000},"page":"1492","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["The Development and Optimization of Lipid-Based Self-Nanoemulsifying Drug Delivery Systems for the Intravenous Delivery of Propofol"],"prefix":"10.3390","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5611-0378","authenticated-orcid":false,"given":"Mohsin","family":"Kazi","sequence":"first","affiliation":[{"name":"Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Athba","family":"Alqahtani","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Majed","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Kayyali Chair for Pharmaceutical Industries, Department of Pharmaceutics, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajaz","family":"Ahmad","sequence":"additional","affiliation":[{"name":"Clinical Pharmacy, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhammad Delwar","family":"Hussain","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, School of Pharmacy, College of Health and Pharmacy, Husson University, Bangor, ME 04401, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0132-558X","authenticated-orcid":false,"given":"Hani","family":"Alothaid","sequence":"additional","affiliation":[{"name":"Department of Basic Sciences, Faculty of Applied Medical Sciences, Al-Baha University, Al Baha 65528, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed S.","family":"Aldughaim","sequence":"additional","affiliation":[{"name":"Research Center, King Fahad Medical City, Riyadh 11451, Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,2,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"77","DOI":"10.1515\/pthp-2019-0014","article-title":"Emulsion Stability of Different Intravenous Propofol Formulations in Simulated Co-Administration with Remifentanil Hydrochloride","volume":"4","author":"Nilsson","year":"2019","journal-title":"Pharm. 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