Solubilization of hydrophobic guest molecules in the monoolein discontinuous QL cubic mesophase and its soft nanoparticles

TY - JOUR

T1 - Solubilization of hydrophobic guest molecules in the monoolein discontinuous QL cubic mesophase and its soft nanoparticles

AU - Efrat, Rivka

AU - Kesselman, Ellina

AU - Aserin, Abraham

AU - Garti, Nissim

AU - Danino, Dganit

PY - 2009/2/3

Y1 - 2009/2/3

N2 - Hydrophobic bioactive guest molecules were solubilized in the discontinuous cubic mesophase (QL) of monoolein. Their effects on the mesophase structure and thermal behavior, and on the formation of soft nanoparticles upon dispersion of the bulk mesophase were studied. Four additives were analyzed. They were classified into two types based on their presumed location within the lipid bilayer and their influence on the phase behavior and structure. Differential scanning calorimetry (DSC), small-angle X-ray scattering (S AXS), polarized light microscopy, cryogenic-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS) were used for the analysis. We found that carbamazepine and cholesterol (type I molecules) likely localize in the hydrophobic domains, but close to the hydrophobic-hydrophilic region. They induce strong perturbation to the mesophase packing by influencing both the order of the lipid acyl chains and interactions between lipid headgroups. This results in significant reduction of the phase transition enthalpy, and phase separation into lamellar and cubic mesophases above the maximum loading capacity. The inclusion of type I molecules in the mesophase also prevents the formation of soft nanoparticles with long-range internal order upon dispersion. In their presence, only vesicles or sponge-like nanoparticles form. Phytosterols and coenzyme Q10 (type II molecules) present only moderate effects. These molecules reside in the hydrophobic domains, where they cannot alter the lipid curvature or transform the QLmesophase into another phase. Therefore, above maximum loading, excess solubilizate precipitates in crystal forms. Moreover, when type Π-loaded QL is dispersed, nanoparticles with long-range order and cubic symmetry (i.e., cubosomes) do form. A model for the growth of the ordered nanoparticles was developed from a series of intermediate structures identified by cryo-TEM. It proposes the development of the internal structure by fusion events between bilayer segments.

AB - Hydrophobic bioactive guest molecules were solubilized in the discontinuous cubic mesophase (QL) of monoolein. Their effects on the mesophase structure and thermal behavior, and on the formation of soft nanoparticles upon dispersion of the bulk mesophase were studied. Four additives were analyzed. They were classified into two types based on their presumed location within the lipid bilayer and their influence on the phase behavior and structure. Differential scanning calorimetry (DSC), small-angle X-ray scattering (S AXS), polarized light microscopy, cryogenic-transmission electron microscopy (cryo-TEM), and dynamic light scattering (DLS) were used for the analysis. We found that carbamazepine and cholesterol (type I molecules) likely localize in the hydrophobic domains, but close to the hydrophobic-hydrophilic region. They induce strong perturbation to the mesophase packing by influencing both the order of the lipid acyl chains and interactions between lipid headgroups. This results in significant reduction of the phase transition enthalpy, and phase separation into lamellar and cubic mesophases above the maximum loading capacity. The inclusion of type I molecules in the mesophase also prevents the formation of soft nanoparticles with long-range internal order upon dispersion. In their presence, only vesicles or sponge-like nanoparticles form. Phytosterols and coenzyme Q10 (type II molecules) present only moderate effects. These molecules reside in the hydrophobic domains, where they cannot alter the lipid curvature or transform the QLmesophase into another phase. Therefore, above maximum loading, excess solubilizate precipitates in crystal forms. Moreover, when type Π-loaded QL is dispersed, nanoparticles with long-range order and cubic symmetry (i.e., cubosomes) do form. A model for the growth of the ordered nanoparticles was developed from a series of intermediate structures identified by cryo-TEM. It proposes the development of the internal structure by fusion events between bilayer segments.

UR - http://www.scopus.com/inward/record.url?scp=61549113807&partnerID=8YFLogxK

U2 - 10.1021/la8016084

DO - 10.1021/la8016084

M3 - 文章

C2 - 18781793

AN - SCOPUS:61549113807

SN - 0743-7463

VL - 25

SP - 1316

EP - 1326

JO - Langmuir

JF - Langmuir

IS - 3

ER -