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

Li X, Zhang Y, Fan Y, Zhou Y, Wang X, Fan C, Liu Y, Zhang Q - Nanoscale Res Lett (2011)

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Haidian District, Beijing 100191, People's Republic of China. yanliu@bjmu.edu.cn.

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.

No MeSH data available.


Related in: MedlinePlus

Concentration of free propofol in the aqueous phase of the commercial lipid emulsion (CLE) and mixed micelle solutions. Values are means ± SD (n = 3). * p > 0.05 vs. mixed micelles with 1% propofol.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3211339&req=5

Figure 3: Concentration of free propofol in the aqueous phase of the commercial lipid emulsion (CLE) and mixed micelle solutions. Values are means ± SD (n = 3). * p > 0.05 vs. mixed micelles with 1% propofol.

Mentions: It was reported that free propofol present in the aqueous phase (outside emulsion droplets and/or micelles) might be an important element causing pain on injection of propofol formulations [36-38]. The content of free propofol present in micellar solution and CLE was therefore determined, respectively. The samples were first separated into lipid (or micelles) and aqueous phases by ultrafiltration. As was seen in Figure 3, the concentration of free propofol in the aqueous phase of CLE containing 1% propofol was found to be 16.87 ± 1.06 μg/mL, whereas 4.69 ± 0.26 μg/mL in the mixed micelles solution with 0.3% propofol, indicating that the concentration of free propofol in mixed micelles was highly significantly lower (by about 72%) than that in CLE (p < 0.001) and that reported previously [39,40]. This might be accounted for by the fact that the micelles are thermodynamically stable system in which the solubilized drug tends to be embed inside micelles until the micelles decompose, just like the results presented in Table 3, whereas emulsion (CLE) is thermodynamically instable system, partial phase inversion or separation led to the leakage of the drug. In addition, there was no significant change in the concentration of free propofol in micelle solution upon dilution (Figure 3), whereas CLE exhibited phase separation upon this stronger dilution. These suggested that propofol-loaded mixed micelles might reduce the incidence and intensity of pain on injection of propofol as compared with CLE and therefore might have favorable compliance to the patients.


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

Li X, Zhang Y, Fan Y, Zhou Y, Wang X, Fan C, Liu Y, Zhang Q - Nanoscale Res Lett (2011)

Concentration of free propofol in the aqueous phase of the commercial lipid emulsion (CLE) and mixed micelle solutions. Values are means ± SD (n = 3). * p > 0.05 vs. mixed micelles with 1% propofol.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3211339&req=5

Figure 3: Concentration of free propofol in the aqueous phase of the commercial lipid emulsion (CLE) and mixed micelle solutions. Values are means ± SD (n = 3). * p > 0.05 vs. mixed micelles with 1% propofol.
Mentions: It was reported that free propofol present in the aqueous phase (outside emulsion droplets and/or micelles) might be an important element causing pain on injection of propofol formulations [36-38]. The content of free propofol present in micellar solution and CLE was therefore determined, respectively. The samples were first separated into lipid (or micelles) and aqueous phases by ultrafiltration. As was seen in Figure 3, the concentration of free propofol in the aqueous phase of CLE containing 1% propofol was found to be 16.87 ± 1.06 μg/mL, whereas 4.69 ± 0.26 μg/mL in the mixed micelles solution with 0.3% propofol, indicating that the concentration of free propofol in mixed micelles was highly significantly lower (by about 72%) than that in CLE (p < 0.001) and that reported previously [39,40]. This might be accounted for by the fact that the micelles are thermodynamically stable system in which the solubilized drug tends to be embed inside micelles until the micelles decompose, just like the results presented in Table 3, whereas emulsion (CLE) is thermodynamically instable system, partial phase inversion or separation led to the leakage of the drug. In addition, there was no significant change in the concentration of free propofol in micelle solution upon dilution (Figure 3), whereas CLE exhibited phase separation upon this stronger dilution. These suggested that propofol-loaded mixed micelles might reduce the incidence and intensity of pain on injection of propofol as compared with CLE and therefore might have favorable compliance to the patients.

Bottom Line: 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.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pharmaceutics, School of Pharmaceutical Sciences, Peking University, Xueyuan Road 38, Haidian District, Beijing 100191, People's Republic of China. yanliu@bjmu.edu.cn.

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.

No MeSH data available.


Related in: MedlinePlus