Preparation and evaluation of novel mixed micelles as nanocarriers for intravenous delivery of propofol

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.

pH-Sensitive Micelles for Targeted Drug Delivery Prepared Using a Novel Membrane Contactor Method

“…Table 3 and Figure 5 Organic Solvent. Numerous organic solvents have been used for micelle preparation, such as methanol, 35 THF, 36 dimethylsulfoxide, 37 N,N-dimethylformamide, and acetone. 38 Although removed by evaporation, solvents may remain as traces in the final formulation, representing a possible risk for human health.…”

Mixed micelles of lipoic acid-chitosan-poly(ethylene glycol) and distearoylphosphatidylethanolamine-poly(ethylene glycol) for tumor delivery

“…Mixed micelles have also shown greater storage stability, attributed to the increased interactions between the hydrophobic chains in the micellar core which stabilize the structure, or to specific polymer characteristics, such as PEG content (Gao et al, 2008;Li et al, 2011;Zheng et al, 2016). Mixed micelles also provide the added advantages of improved drug loading and cellular uptake, as demonstrated for a range of hydrophobic drugs (Attia et al, 2013;Butt et al, 2012;Cao et al, 2016;Kahook et al, 2010;Yang, 2010).…”

“…Improved stability has previously been associated with mixed PEG-based micelles, such as poly(histidine)-PEG/DSPE-PEG and PEG-DSPE/TPGS Wu et al, 2013). Increased storage stability of mixed micelles has been attributed to the increased interactions between the hydrophobic chains in the micellar core which would stabilize the structure, or to specific polymer characteristics, such as PEG content (Gao et al, 2008;Li et al, 2011;Zheng et al, 2016). Drug-loading increased DSPE-PEG…”

6-Shogaol Rich Ginger Oleoresin Loaded Mixed Micelles Enhances in Vitro Cytotoxicity on McF-7 Cells and in Vivo Anticancer Activity Against Dal Cells

“…In addition, mixed micelles of 10-400 nm are advantageous for passive targeting into solid tumors by virtue of the enhanced permeability and retention (EPR) effect [24]. Such systems have been applied for delivery of various anticancer drugs such as doxorubicin, propofol, docetaxel and gambogic acid [25][26][27][28][29].…”