Determination of critical micelle concentration of lipopolymers and other amphiphiles: Comparison of sound velocity and fluorescent measurements

Aba Priev, Samuel Zalipsky, Rivka Cohen, Yechezkel Barenholz*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


Critical micelle concentration (cmc) is an important parameter for preparing, solubilizing, and characterizing liposomes, surfactants, and other self-aggregating amphiphiles. We present a comparison between a direct, nondestructive method to determine cmc, in which sound velocity is measured as a function of the concentration of amphiphile, and a commonly used fluorescent method based on two fluorophores (1,6-diphenylhexa-1,3,5-triene (DPH) and 8-anilinonaphthalene-1-sulfonate (ANS)). The ultrasonic method involves accurate measurement of the sound velocity in the amphiphile dispersion and determination of the concentration corresponding to the maximum change in a gradient in the sound velocity. This method does not use a probe (like DPH or ANS), and therefore the contribution of artifacts related to impurities is minimal. Initially we used the ultrasonic method to determine the cmc's, in several media, of three typical detergents, sodium dodecyl sulfate (SDS), Triton X-100, and Cremophor EL, for which highly reliable cmc values have been reported. The ultrasonic instrumentation, based on a cylindrical resonator method, gives precise and accurate results for the general range of cmc values for detergents (10-3- 102 mM) and reflects changes in hydration and compressibility of the amphiphile. We then applied this ultrasonic method to determine the cmc's of two series of PEGylated lipopolymers used for steric stabilization of liposomes: the neutral distearoyl glycerol and the negatively charged distearoyl phosphatidylethanolamine, both covalently attached to poly(ethylene glycol) (PEG) of Mw 750, 2000, 5000, or 12000. The cmc's for these PEGylated lipopolymers were in the range 0.008 0.025 mM. cmc values increased 2.5-fold with increase in length of the PEG chain from 15 to 271 oxyethylene units, cmc values were the same when the linker connecting the PEG and the distearoyl moieties was negatively charged or neutral. In a comparative study, the ultrasonic method proved to be superior to commonly used methods in accuracy, speed, and applicability to both ionic and nonionic surfactants, in both aqueous and nonaqueous media.

Original languageAmerican English
Pages (from-to)612-617
Number of pages6
Issue number3
StatePublished - 5 Feb 2002


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