Abstract
Novel mixed polymeric micelles formed from biocompatible polymers, poly(ethylene glycol)-poly(lactide) (mPEG-PLA) and polyoxyethylene-660-12-hydroxy stearate (Solutol HS15), were fabricated and used as a nanocarrier for solubilizing poorly soluble anesthetic drug propofol. The solubilization of propofol by the mixed micelles was more efficient than those made of mPEG-PLA alone. Micelles with the optimized composition of mPEG-PLA/Solutol HS15/propofol = 10/1/5 by weight had particle size of about 101 nm with narrow distribution (polydispersity index of about 0.12). Stability analysis of the mixed micelles in bovine serum albumin (BSA) solution indicated that the diblock copolymer mPEG efficiently protected the BSA adsorption on the mixed micelles because the hydrophobic groups of the copolymer were efficiently screened by mPEG, and propofol-loaded mixed micelles were stable upon storage for at least 6 months. The content of free propofol in the aqueous phase for mixed micelles was lower by 74% than that for the commercial lipid emulsion. No significant differences in times to unconsciousness and recovery of righting reflex were observed between mixed micelles and commercial lipid formulation. The pharmacological effect may serve as pharmaceutical nanocarriers with improved solubilization capacity for poorly soluble drugs.
Highlights
Propofol, chemically named 2,6-diisopropylphenol, is a highly effective and rapid intravenous anesthetics, which has gained increasing popularity in anesthesia in clinic
One main concern following the use of polymeric micelles for drug carriers is the severe dilution they undergo in the biological environment
The trend that the critical micellization concentration (CMC) of mPEG5000-PLA4800 increased with the increase of Solutol HS15 content was observed, which was in accordance with our previous report [13]
Summary
Chemically named 2,6-diisopropylphenol, is a highly effective and rapid intravenous anesthetics, which has gained increasing popularity in anesthesia in clinic. A low incidence of postoperative nausea and vomiting was observed [1,2] It has some drawbacks such as poor water miscibility (150 μg/L) [3] and high lipophilicity (logP = 4.16) [4]. In view of the clinical importance of propofol, the alternative formulations such as oil/water emulsion consisting of soya bean oil, glycerol, and egg size with a narrow distribution. They can protect drugs against oxidation in vitro and premature degradation in vivo owing to their core-shell architecture [19,20]. There has been an urgent quest to develop an ideal polymeric micelles formulation that can solubilize propofol efficiently and solve some of the aforementioned problems
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
