Physicochemical Characterization and Pharmacological Evaluation of Novel Propofol Micelles with Low-Lipid and Low-Free Propofol
Yongchao Chu,
Tao Sun,
Zichen Xie,
Keyu Sun,
Chen Jiang
Affiliations
Yongchao Chu
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Research Center on Aging and Medicine, Fudan University, Shanghai 201203, China
Tao Sun
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Research Center on Aging and Medicine, Fudan University, Shanghai 201203, China
Zichen Xie
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Research Center on Aging and Medicine, Fudan University, Shanghai 201203, China
Keyu Sun
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Research Center on Aging and Medicine, Fudan University, Shanghai 201203, China
Chen Jiang
Department of Pharmaceutics, School of Pharmacy, Key Laboratory of Smart Drug Delivery (Ministry of Education), Minhang Hospital, State Key Laboratory of Medical Neurobiology, MOE Frontiers Center for Brain Science, Research Center on Aging and Medicine, Fudan University, Shanghai 201203, China
We developed safe and stable mixed polymeric micelles with low lipids and free propofol for intravenous administration, to overcome the biological barrier of the reticuloendothelial system (RES), reduce pain upon injection, and complications of marketed propofol formulation. The propofol-mixed micelles were composed of distearoyl-phosphatidylethanolamine-methoxy-poly (ethylene glycol 2000) (DSPE mPEG2k) and Solutol HS 15 and were optimized using Box Behnken design (BBD). The optimized formulation was evaluated for globule size, zeta potential, loading content, encapsulation efficiency, pain on injection, histological evaluation, hemolysis test, in vivo anesthetic action, and pharmacokinetics, in comparison to the commercialized emulsion Diprivan. The optimized micelle formulation displayed homogenous particle sizes, and the free drug concentration in the micelles was 60.9% lower than that of Diprivan. The paw-lick study demonstrated that propofol-mixed micelles significantly reduced pain symptoms. The anesthetic action of the mixed micelles were similar with the Diprivan. Therefore, we conclude that the novel propofol-mixed micelle reduces injection-site pain and the risk of hyperlipidemia due to the low content of free propofol and low-lipid constituent. It may be a more promising clinical alternative for anesthetic.
