Abstract
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.
Highlights
Propofol (2,6-diisopropylphenol) is a short-acting sedative and hypnotic agent that is most frequently administered as an intravenous anesthetic in clinics
In order to replace the high level of lipid component and reduce the concentration of free propofol, this study presents a novel micelles formulation based on DSPE mPEG2k and Solutol HS 15
This study evaluates the new formulation of the propofol-mixed micelle for size distribution, zeta potential, pH, osmolarity, morphology, and the degree of free propofol in the aqueous phase
Summary
Propofol (2,6-diisopropylphenol) is a short-acting sedative and hypnotic agent that is most frequently administered as an intravenous anesthetic in clinics. The copolymer micelle, as a novel carrier, exhibits many unique advantages, such as lessened undesirable effects of drugs, increased drug loading and it is stable during storage [18,19]. They are able to improve drug stability by protecting the molecules from premature degradation due to the core–shell nanostructure [20,21,22]. In order to replace the high level of lipid component and reduce the concentration of free propofol, this study presents a novel micelles formulation based on DSPE mPEG2k and Solutol HS 15. In vivo efficacy and pharmacokinetic studies were conducted in rats
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
