Positron annihilation lifetime spectroscopy (PALS): a probe for molecular organisation in self-assembled biomimetic systems.

Positron annihilation lifetime spectroscopy (PALS) has been shown to be highly sensitive to conformational, structural and microenvironmental transformations arising from subtle geometric changes in molecular geometry in self-assembling biomimetic systems. The ortho-positronium (oPs) may be considered an active probe that can provide information on intrinsic packing and mobility within low molecular weight solids, viscous liquids, and soft matter systems. In this perspective we provide a critical overview of the literature in this field, including the evolution of analysis software and experimental protocols with commentary upon the practical utility of PALS. In particular, we discuss how PALS can provide unique insight into the macroscopic transport properties of several porous biomembrane-like nanostructures and suggest how this insight may provide information on the release of drugs from these matrices to aid in developing therapeutic interventions. We discuss the potentially exciting and fruitful application of this technique to membrane dynamics, diffusion and permeability. We propose that PALS can provide novel molecular level information that is complementary to conventional characterisation techniques.

Application of positron annihilation lifetime spectroscopy (PALS) to study the nanostructure in amphiphile self-assembly materials: phytantriol cubosomes and hexosomes.

Self-assembled amphiphile nanostructures of colloidal dimensions such as cubosomes and hexosomes are of interest as delivery vectors in pharmaceutical and nanomedicine applications. Translation would be assisted through a better of understanding of the effects of drug loading on the internal nanostructure, and the relationship between this nanostructure and drug release profile. Positron annihilation lifetime spectroscopy (PALS) is sensitive to local microviscosity and is used as an in situ molecular probe to examine the Q2 (cubosome) → H2 (hexosome) → L2 phase transitions of the pharmaceutically relevant phytantriol-water system in the presence of a model hydrophobic drug, vitamin E acetate (VitEA). It is shown that the ortho-positronium lifetime (τ) is sensitive to molecular packing and mobility and this has been correlated with the rheological properties of individual lyotropic liquid crystalline mesophases. Characteristic PALS lifetimes for L2 (τ4∼ 4 ns) ∼ H2 (τ4∼ 4 ns) > Q(2 Pn3m) (τ4∼ 2.2 ns) are observed for the phytantriol-water system, with the addition of VitEA yielding a gradual increase in τ from τ∼ 2.2 ns for cubosomes to τ∼ 3.5 ns for hexosomes. The dynamic chain packing at higher temperatures and in the L2 and H2 phases is qualitatively less "viscous", consistent with rheological measurements. This information offers increased understanding of the relationship between internal nanostructure and species permeability.

Packing and mobility of hydrocarbon chains in phospholipid lyotropic liquid crystalline lamellar phases and liposomes: characterisation by positron annihilation lifetime spectroscopy (PALS).

Lipid lamellar mesophases and their colloidal dispersions (liposomes) are increasingly being deployed in vivo as drug delivery vehicles, and also as models of biological membranes in fundamental biophysics studies. The permeability and diffusion of small molecules such as drugs is accommodated by a change in local curvature and molecular packing (mesophase behaviour) of the bilayer membrane molecules. Positron annihilation lifetime spectroscopy (PALS) is capable of providing in situ molecular level information on changes in free volume and void space arising from such changes in a non-perturbative manner. In this work PALS was used to systematically characterise the temperature-induced melting transitions (Tm) of saturated and unsaturated phospholipid-water systems while systematically varying lipid chain length, as both bulk lamellar mesophase and as aqueous colloidal dispersions (liposomes). A four-component fit of the data was used that provides separate PALS lifetimes for the aqueous (τ3) and organic domains (τ4). The oPs lifetime (τ4), for the lamellar phases of DSPC (C18:0), DPPC (C16:0), DMPC (C14:0) and DLPC (C12:0) was found to be independent of chain length, with characteristic lifetime value τ4 ∼ 3.4 ns. τ4 is consistently larger in the dispersed liposomes compared to the bulk mesophases, suggesting that the hydrocarbon chains are more mobile. The use of contemporary and consistent analytical approaches as described in this study is the key to future deployment of PALS to interrogate the in situ influence of drugs on membrane and cellular microenvironments.

Probing the amphiphile micellar to hexagonal phase transition using Positron Annihilation Lifetime Spectroscopy.

Positron Annihilation Lifetime Spectroscopy (PALS) has been utilised only sparingly for structural characterisation in self assembled materials. Inconsistencies in approaches to experimental configuration and data analysis between studies has complicated comparisons between studies, meaning that the technique has not provided a cohesive data set across the study of different self assembled systems that advance the technique towards an important tool in soft matter research. In the current work a systematic study was conducted using ionic and non-ionic micellar systems with increasing surfactant concentration to probe positron behaviour on changes between micellar phase structures, and data analysed using contemporary approaches to fit four component spectra. A characteristic orthopositronium lifetime (in the organic regions) of 3.5±0.2 ns was obtained for the hexagonal phase for surfactants with C12 alkyl chains. Chemical quenching of the positron species was also observed for systems with ionic amphiphiles. The application of PALS has also highlighted an inconsistency in the published phase diagram for the octa(ethylene oxide) monododecyl ether (C12EO8) system. These results provide new insight into how the physical properties of micellar systems can be related to PALS parameters and means that the PALS technique can be applied to other more complex self-assembled amphiphile systems.

Positron annihilation lifetime spectroscopy (PALS) as a characterization technique for nanostructured self-assembled amphiphile systems.

Positron annihilation lifetime spectroscopy (PALS) has potential as a novel rapid characterization method for self-assembly amphiphile systems; however, a lack of systematic correlation of PALS parameters with structural attributes has limited its more widespread application. In this study, using the well-characterized phytantriol/water and the phytantriol/vitamin E acetate/water self-assembly amphiphile systems, the impact of systematic structural changes controlled by changes in composition and temperature on PALS parameters has been studied. The PALS parameters (orthopositronium (oPs) lifetime and intensity signatures) were shown to be sensitive to the molecular packing and mobility of the self-assembled lipid molecules in various lyotropic liquid crystalline phases, enabling differentiation between liquid crystalline structures. The oPs lifetime, related to the molecular packing and mobility, is correlated with rheological properties of the individual mesophases. The oPs lifetime links the lipid chain packing and mobility in the various mesophases to resultant macroscopic properties, such as permeability, which is critical for the use of these mesophase structures as diffusion-controlled release matrices for active liposoluble compounds.

Impurities in commercial phytantriol significantly alter its lyotropic liquid-crystalline phase behavior.

The lyotropic liquid-crystalline phase behavior of phytantriol is receiving increasing interest in the literature as a result of similarities with glyceryl monooleate, despite its very different molecular structure. Some differences in the phase-transition temperature for the bicontinuous cubic to reverse hexagonal phase have been reported in the literature. In this study, we have investigated the influence that the commercial source and hence the purity has on the lyotropic phase behavior of phytantriol. Suppression of the phase-transition temperatures (by up to 15 degrees C for the bicontinuous cubic to reverse hexagonal phase transition) is apparent with lower-purity phytantriol. In addition, the composition boundaries were also found to depend significantly on the source and purity of phytantriol, with the bicontinuous cubic phase + excess water boundary occurring at a water content above that reported previously (i.e., >5% higher). Both the temperature and compositional changes in phase boundaries have significant implications on the use of these materials and highlight the impact that subtle levels of impurities can play in the phase behavior of these types of materials.