Melting regime of the anionic phospholipid DMPG: new lamellar phase and porous bilayer model.

Aqueous dispersions of the anionic phospholipid dimyristoyl phosphatidylglycerol (DMPG) at pH above the apparent pK of DMPG and concentrations in the interval 70-300 mM have been investigated by small (SAXS) and wide-angle X-ray scattering, differential scanning calorimetry, and polarized optical microscopy. The order-disorder transition of the hydrocarbon chains occurs along an interval of about 10 degrees C (between T(m)(on) approximately 20 degrees C and T(m)(off) approximately 30 degrees C). Such melting regime was previously characterized at lower concentrations, up to 70 mM DMPG, when sample transparency was correlated with the presence of pores across the bilayer. At higher concentrations considered here, the melting regime persists but is not transparent. Defined SAXS peaks appear and a new lamellar phase L(p) with pores is proposed to exist above 70 mM DMPG, starting at approximately 23 degrees C (approximately 3 degrees C above T(m)(on)) and losing correlation after T(m)(off). A new model for describing the X-ray scattering of bilayers with pores, presented here, is able to explain the broad band attributed to in-plane correlation between pores. The majority of cell membranes have a net negative charge, and the opening of pores across the membrane tuned by ionic strength, temperature, and lipid composition is likely to have biological relevance.

Pressure effects on lipidic direct phases: the dodecyl trimethyl ammonium chloride-water system.

The direct lyotropic polymorphism of dodecyltrimethylammonium chloride (DTAC) was investigated by synchrotron X-ray diffraction at different water concentrations under compression up to 2 kbar, i.e., in the pressure intermediate range where interesting biophysical transformations occur and the functional characteristics of cell membranes are altered. The results show that pressure induces the transition from the hexagonal phase to the micellar Pm3n cubic phase in hydrated samples (c between 0.5 and 0.6, c being the weight concentration of lipid in the mixture) and the transition from the bicontinuous Ia3d cubic phase to the hexagonal phase in drier samples (c = 0.8). By increasing the pressure on very dry samples, a lamellar L(alpha) phase was observed to form transitorily at the Ia3d cubic-hexagonal phase transition. Phase compressibility and then the lipid and water partial molecular compressibilities were derived as a function of pressure and concentration. As a result, we assessed the very low compressibility of the hydration water within the lipid phases, and we demonstrated that the compressibility of DTAC is very dependent on pressure. Moreover, the molecular parameters of DTAC calculated in the different phases during compression confirmed that pressure induces small but continuous conformational changes, definitely different from the large changes observed in lipid molecules forming type II structures.

Solid lipid nanoparticles as delivery systems for bromocriptine.

PURPOSE: The present investigation describes a formulative study for the development of innovative drug delivery systems for bromocriptine. METHODS: Solid lipid nanoparticles (SLN) based on different lipidic components have been produced and characterized. Morphology and dimensional distribution have been investigated by electron microscopy and Photon Correlation Spectroscopy. The antiparkinsonian activities of free bromocriptine and bromocriptine encapsulated in nanostructured lipid carriers were evaluated in 6-hydroxydopamine hemilesioned rats, a model of Parkinson's disease. RESULTS: Tristearin/tricaprin mixture resulted in nanostructured lipid carriers with stable mean diameter up to 6 months from production. Bromocriptine was encapsulated with high entrapment efficiency in all of the SLN samples, particularly in the case of tristearin/tricaprin mixture. Bromocriptine encapsulation did not change nanoparticle dimensions. In vitro release kinetics based on a dialysis method demonstrated that bromocriptine was released in a prolonged fashion for 48 h. Tristearin/tricaprin nanoparticles better controlled bromocriptine release. Both free and encapsulated bromocriptine reduced the time spent on the blocks (i.e. attenuated akinesia) in the bar test, although the action of encapsulated bromocriptine was more rapid in onset and prolonged. CONCLUSIONS: It can be concluded that nanostructured lipid carriers encapsulation may represent an effective strategy to prolong the half-life of bromocriptine.

Cubosome dispersions as delivery systems for percutaneous administration of indomethacin.

PURPOSE: The present study concerns the production and characterization of monooleine (MO) dispersions as drug delivery systems for indomethacin, taken as model anti-inflammatory drug. METHODS: Dispersions were produced by emulsification and homogenization of MO and poloxamer in water. Morphology and dimensional distribution of the disperse phase have been characterized by cryo-transmission electron microscopy and photon correlation spectroscopy, respectively. X-ray diffraction has been performed to determine the structural organization of the disperse phase. Sedimentation field flow fractionation (SdFFF) has been performed to investigate drug distribution in the dispersion. An in vitro diffusion study was conducted by Franz cell associated to stratum corneum epidermis membrane on cubosome dispersions viscosized by carbomer. In vivo studies based on skin reflectance spectrophotometry and tape stripping were performed to better investigate the performance of cubosome as indomethacin delivery system. RESULTS: Microscopy studies showed the coexistence of vesicles and cubosomes. X-ray diffraction revealed the presence of a bicontinuous cubic phase of spatial symmetry Im3m (Q229). SdFFF demonstrated that no free drug was present in the dispersion. Indomethacin incorporated in viscosized MO dispersions exhibited a lower flux with respect to the analogous formulation containing the free drug in the aqueous phase and to the control formulation based on carbomer gel. Reflectance spectroscopy demonstrated that indomethacin incorporated into MO dispersions can be released in a prolonged fashion. Tape-stripping experiments corroborated this finding. CONCLUSIONS: MO dispersions can be proposed as nanoparticulate systems able to control the percutaneous absorption of indomethacin.