Effect of the electrostatic charge on the mechanism inducing liposome solubilization: a kinetic study by synchrotron radiation SAXS.

The anionic surfactant sodium dodecyl sulfate (SDS) was used to induce the initial steps of the solubilization of liposomes. The structural transformations as well as the kinetics associated with this initial period were studied by means of time-resolved small-angle X-ray scattering (SAXS) using a synchrotron radiation source. Neutral and electrically charged (anionic and cationic) liposomes were used to investigate the effect of the electrostatic charges on the kinetics of these initial steps. The mechanism that induces the solubilization process consisted of adsorption of surfactant on the bilayers and desorption of mixed micelles from the liposomes surface to the aqueous medium. In all cases the time needed for desorption of the first mixed micelles was shorter than that for complete adsorption of the surfactant on the liposomes surface. The present work demonstrates that adsorption of the SDS molecules on negatively charged liposomes was slower and release of mixed micelles from the surface of these liposomes was faster than for neutral liposomes. In contrast, in the case of positively charged liposomes, the adsorption and release processes were, respectively, faster and slower than those for neutral vesicles.

[Detection of the cutaneous melanomas, their metastasis and relapses by scintigraphies with 99MTC-HMPAO]. / Detección de melanomas cutáneos, sus metástasis y recidivas mediante gammagrafías con 99mTc-HMPAO.

A pilot study was carried out in the Nuclear Medicine Department of the National Institute of Oncology and Radiobiology to learn the diagnostic efficacy of the 99mTc-HMPAO scintigraphy in the detection of cutaneous melanoma, distant and local metastases, in patients with a confirmed histological diagnosis. The planar and/or SPECT scintigraphy was performed in 17 patients and revealed 90% sensitivity for the detection of the disease. We calculated the tumor/background index in all the images obtained and found a value greater than 1 in every case. Thus, we can affirm that the 99mTc-HMPAO accumulation in tumors was higher than the background in all cases. We recommend that this procedure be considered in the follow up of these patients as a new diagnostic method which is very useful in the determination of the patient stage and prognostic evaluation.

Influence of ceramides in the solubilization of stratum corneum lipid liposomes by C(12)-betaine/sodium dodecyl sulfate mixtures.

The solubilization of liposomes modeling the stratum corneum (SC) lipid composition and those obtained varying the proportion of ceramides by means of dodecyl betaine (C(12)-Bet)/sodium dodecyl sulfate (SDS) mixtures was studied. The surfactant/lipid molar ratios (Re) and the bilayer/aqueous phase partition coefficients (K) were determined by monitoring the changes in the static light scattering of the system during solubilization. The fact that the free surfactant concentration was always similar to its critical micelle concentration (CMC) indicates that the liposome solubilization was mainly ruled by the formation of mixed micelles. The mole fraction of the zwitterionic component (X(zwitter)) of 0.4 showed the lowest ability to saturate or solubilize liposomes, although exhibiting the highest degree of partitioning into liposomes. This X(zwitter) corresponded to the highest derivation of the CMCs of these mixtures (negative synergism) and to the highest reduction in the skin irritation with respect to the anionic component. Higher and lower proportion of ceramides in the mixture led to a fall and to a rise in both the activity and the partitioning of a specific surfactant mixture (X(zwitter)=0.4). This finding could be related to the recently reported dependences of the level of ceramides in skin and function barrier abnormalities. Comparison of the present Re and K values with those reported for phosphatidylcholine (PC) liposomes shows that, although SC liposomes were more resistant to the action of surfactant mixtures, the surfactant partitioning into SC bilayers was similar to that reported for PC ones in all cases.

Influence of the level of ceramides on the permeability of stratum corneum lipid liposomes caused by a C12-betaine/sodium dodecyl sulfate mixture.

The sublytic interactions of a mixture of N-dodecyl-N, N-dimethylbetaine dodecyl betaine (C12-Bet)/sodium dodecyl sulfate (SDS) (mole fraction of the zwitterionic surfactant=0.6) with stratum corneum (SC) lipid liposomes varying the proportion of ceramides type III (Cer) were investigated. The surfactant/lipid molar ratios (Re) and the bilayer/aqueous phase partition coefficients (K) were determined by monitoring the changes in the fluorescence intensity of liposomes due to the 5(6) carboxyfluorescein (CF) released from the interior of vesicles. The fact that the free surfactant mixture concentration was always lower than its critical micelle concentration indicates that permeability changes were ruled by the action of surfactant monomers in all cases. Higher and lower Cer proportions than that of the SC lipids led to a fall and to a rise in the activity of the surfactant mixture on these bilayer structures. However, the surfactant partitioning into liposomes (or affinity with these bilayer structures) increased as the proportion of Cer increased up to the highest value was achieved for a Cer proportion similar to that in the SC lipids (about 40-45%). Thus, at low Cer proportions the ability of the surfactant mixture to alter the permeability of these bilayer structures was higher than that for liposomes approximating the SC lipid composition despite their reduced partitioning into liposomes. These findings are in agreement with the recently reported dependencies of the level of ceramides in skin lipids and function barrier abnormalities and could explain in part these dependencies.

[Radionuclide study of cutaneous melanomas with 99m Tc-HMPAO: visualization of metastases and recurrence]. / Estudio gammagráfico de los melanomas cutáneos con 99m Tc-HMPAO: visualización de metástasis y recidivas.

Malignant cutaneous melanoma (MCM) is a very aggressive disease that becomes in a true problem of health because of the increase in the last 5 years. In the present paper, authors report the detection of the tumor, metastases and recurrences mean 99mTc HMPAO. We presented 5 cases of MCM patients and observed the radiopharmaceutical uptake in skin, nodules and recurrent tumor lesions. Because of the number of patients was limited, authors recommended the research with a lot of patients. The gammagraphic studies could be very important for the staging of the disease and early detection of metastases and recurrent lesions.

Solubilization of phosphatidylcholine liposomes by the amphoteric surfactant dodecyl betaine.

The interaction of the amphoteric surfactant N-dodecyl-N,N-dimethylbetaine (C12-Bet) with phosphatidylcholine (PC) liposomes was investigated. Permeability alterations were detected as a change in 5(6)-carboxyfluorescein (CF) released from the interior of vesicles and bilayer solubilization as a decrease in the static light-scattering (SLS) of the system. At sublytic level a initial maximum in the bilayer/water partitioning (K) followed by an abrupt decrease of this parameter occurred as the surfactant to lipid molar ratio (Re) rose. At lytic level a direct dependence was established between both parameters. The fact that the free surfactant concentration at sublytic and lytic levels showed values lower than and similar to its critical micelle concentration indicates that permeability alterations and solubilization were determined, respectively, by the action of surfactant monomer and by the formation of mixed micelles. A direct correlation occurred in the initial interaction steps (up to 50% CF release) between the growth of vesicles their fluidity and Re. A similar direct dependence was established during solubilization (up to 30% SLS) between the fall in both the surfactant-lipid aggregate size, the SLS of the system and Re. This surfactant showed higher capacity to solubilize PC liposomes than that reported by the commonly used non-ionic surfactants octyl glucoside and Triton X-100 and by the anionic one sodium dodecyl sulfate.