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The most common way to analyse PALS spectra involves fitting a parameter-dependent model to the experimental data. Traditionally, this fit involves local non-linear optimisation routines that depend on a reasonable initial guess for the searched parameters. This, together with the fact that very different sets of parameters may yield indistinguishably good fits for a given experimental spectrum, gives rise to ambiguities in the data analysis in most but the simplest cases. In order to alleviate these difficulties, a computer program named PAScual was developed that incorporates 2 advanced algorithms to provide a robust fitting tool: on the one hand, it incorporates a global non-linear optimisation routine based on the Simulated Annealing algorithm and, on the other hand, it yields information on the reliability of the results by means of a Markov Chain Monte-Carlo Bayesian Inference method. In this work the methods used in PAScual are described and tested against both simulated and experimental spectra, comparing the results with those from the well-established program LTv9. The examples focus on the type of complex data that results from the study of self-assembled amphiphile materials containing co-existing aqueous and hydrocarbon regions.

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) > Q2Pn3m (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.

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.

Self-assembled amphiphile systems are utilized in a wide variety of applications including drug delivery and energy storage. Nano-scale physical and chemical interactions govern the packing of self-assembled amphiphilic molecules, resulting in thermodynamically stable phases of defined geometries. Possible phases include micellar, hexagonal, cubic, lamellar and sponge phases. The internal nano-structure of the amphiphile self-assembly materials plays an important role in the properties of these systems and their application. To date small angle x-ray scattering (SAXS) has been the most common technique used to characterise their structure. We explore positron annihilation lifetime spectroscopy (PALS) as an alternative and/or complementary technique for this purpose, using the phytantriol/water system. While PALS is a well established technique for characterising many materials, the coexistence of aqueous and hydrophobic regions in a soft self-assembled amphiphile material poses a challenge to the analysis and interpretation of the results. In order to alleviate these difficulties we developed a computer program for general-purpose PALS data analysis called PAScual. Amongst the most salient features of this new code are the possibility to perform bounded fits and the option of using advanced algorithms to provide a more robust and unbiased fit: on the one hand, it incorporates a global nonlinear optimisation routine based on the Simulated Annealing algorithm and, on the other hand it gives information on the reliability of the results by means of a Markov Chain Monte-Carlo Bayesian Inference method. In this work we present the newly developed PALS data analysis techniques as well as the results for the phytantriol/water system, comparing them with additional data obtained from complementary techniques.

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.

Self-assembled amphiphile systems are utilized in a wide variety of applications including drug delivery and energy storage. Nano-scale physical and chemical interactions govern the packing of self-assembled amphiphilic molecules, resulting in thermodynamically stable phases of defined geometries. Possible phases include micellar, hexagonal, cubic, lamellar and sponge phases. The internal nano-structure of the amphiphile self assembly materials play an important role in the properties of these systems and their application. To date small angle x-ray scattering (SAXS) has been the most common technique used to characterise their structure. Positron annihilation lifetime spectroscopy (PALS) offers a possible alternative technique as it is sensitive to both the internal cavities and the intermolecular forces and in combination with SAXS, may provide more detailed structural information such as trends with composition and temperature variations. The phase behaviour of a bulk phytantriol sample, consisting of 33 % w/w water was explored using PALS, and it was found that PALS was sensitive to phase transitions from bicontinuous cubic (Pn3m) to reversed hexagonal (H2) to reversed micellar (L2) phases. These boundaries agreed well with SAXS data. Trends observed for the PALS parameters ι3 and I3 as a function of temperature largely supports the concept that the ortho-positronium is annihilating in the organic regions of the self-assembled structure. However, further investigation is required. We have also developed an innovative data analysis technique to analyse PALS spectra for pore information, with the aim of minimising operator bias and error, which leads to better quantitative comparison of PALS results between laboratories.© (2007) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.