Browsing by Author "Boyd, BJ"

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    Controlling the nanostructure of gold nanorod-lyotropic liquid-crystalline hybrid materials using near-infrared laser irradiation
    (American Chemical Society, 2012-10-09) Fong, WK; Hanley, TL; Thierry, B; Kirby, N; Waddington, LJ; Boyd, BJ
    Lipid-based liquid-crystalline matrixes provide a unique prospect for stimuli-responsive nanomaterials, attributed to the ability to effect self-assembly of the lipids at the molecular level. Differences in liquid crystal nanostructure have previously been shown to change drug diffusion and hence release, with research progressing toward the use of in situ changes to nanostructure to control drug release. Toward this goal, we have previously communicated the ability to switch between nonlamellar structures using gold nanorod (GNR)-phytantriol-based liquid-crystalline hybrid nanomaterials as near-infrared light responsive systems (Fong et al. Langmuir 2010, 26, 6136-6139). In this study, the effect of laser activation on matrix nanostructure with changes in a number of system variables including lipid composition, GNR aspect ratio, GNR concentration, and laser pulse time were investigated. The nanostructure of the matrix was followed using small-angle X-ray scattering, while both cryoFESEM and cryoTEM were used to visualize the effect of GNR incorporation into the liquid crystal nanostructure. The system response was found to be dependent on all variables, thus demonstrating the potential of these nanocomposite materials as reversible "on-demand" drug delivery applications. © 2012, American Chemical Society.
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    Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid a stimulate robust cellular and humoral immune responses
    (Elsevier, 2013-01-10) Rizwan, SB; McBurney, WT; Young, K; Hanley, TL; Boyd, BJ; Rades, T; Hook, S
    New generation vaccines increasingly utilize highly purified peptides and proteins as the target antigen, however these are often poorly immunogenic. One of the most promising strategies for improving immunogenicity of such subunit vaccines is through incorporation into particulate carriers. Here we report the preparation, physicochemical characterization and in vivo immunological activity of cubosomes, a novel lipid-based nanostructured particulate carrier, modified to include the Toll-like receptor agonists monophosphoryl lipid A and imiquimod. The immunological activity of cubosome formulations was compared to that of liposome and alum formulations. Sustained release of the model antigen ovalbumin (Ova) was observed in vitro and in vivo from cubosomes. Cubosomes + adjuvants induced robust CD8(+) and CD4(+) T cell proliferation and interferon-gamma production, as well as the production of Ova-specific antibodies. Cubosomes+ adjuvants were more efficient at generating Ova-specific cellular responses and were equally as effective in generating humoral responses when compared to liposomes + adjuvants and alum. Overall, the results show that cubosomes have the potential to act as effective sustained release vaccine delivery systems. © 2013, Elsevier Ltd.
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    External manipulation of nanostructure in photoresponsive lipid depot matrix to control and predict drug release in vivo
    (Elsevier B.V., 2016-04-28) Fong, WK; Hanley, TL; Thierry, B; Hawley, A; Boyd, BJ; Landersdorfer, CB
    On-demand drug delivery systems are highly promising to control the time-course of drug release and ultimately optimize drug concentration time profiles in patients. Lipid based lyotropic liquid crystalline mesophases have demonstrated exceptional responsiveness to external stimuli such as heat, pH and light. Our objective was to quantitatively characterize the time-course of light activated drug release from near infrared (NIR) activated photothermal systems using ex vivo and in vivo studies. Photoresponsive hybrid gold nanorod-liquid crystalline matrices were prepared and loaded into custom-made implants which were inserted into subcutaneous tissues in rats. Time resolved SAXS studies showed the abdomen to be the best site of implantation to achieve in vivo activation of the subcutaneous dose from by the NIR laser. External control of drug release was achieved via NIR laser light and plasma concentrations of the model drug were determined over time. Laser activation achieved a phase change of the photoresponsive formulations and thereby a considerable change in the rate of drug release. Population pharmacokinetic modeling of all results simultaneously revealed a two stage release process unique to these liquid crystalline matrices. The developed structural model was able to successfully describe also the results of our previous study in 2009 where a change in temperature was utilized to trigger subcutaneous drug release. Thus, modeling of the data proved to be a valuable analytical tool which provided a quantitative understanding of the time-course of drug release in vivo and will be essential in the development of these matrices as on-demand release systems. © 2016, Elsevier B.V.
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    Formation of liquid-crystalline structures in the bile salt–chitosan system and triggered release from lamellar phase bile salt–chitosan capsules
    (American Chemical Society, 2014-07-22) Tangso, KJ; Lindberg, S; Hartley, PG; Knott, RB; Spicer, P; Boyd, BJ
    Nanostructured capsules comprised of the anionic bile salt, sodium taurodeoxycholate (STDC), and the biocompatible cationic polymer, chitosan, were prepared to assess their potential as novel tailored release nanomaterials. For comparison, a previously studied system, sodium dodecyl sulfate (SDS), and polydiallyldimethylammonium chloride (polyDADMAC) was also investigated. Crossed-polarizing light microscopy (CPLM) and small-angle X-ray scattering (SAXS) identified the presence of lamellar and hexagonal phase at the surfactant–polymer interface of the respective systems. The hydrophobic and electrostatic interactions between the oppositely charged components were studied by varying temperature and salt concentration, respectively, and were found to influence the liquid-crystalline nanostructure formed. The hexagonal phase persisted at high temperatures, however the lamellar phase structure was lost above ca. 45 °C. Both mesophases were found to dissociate upon addition of 4% NaCl solution. The rate of release of the model hydrophilic drug, Rhodamine B (RhB), from the lamellar phase significantly increased in response to changes in the solution conditions studied, suggesting that modulating the drug release from these bile salt–chitosan capsules is readily achieved. In contrast, release from the hexagonal phase capsules had no appreciable response to the stimuli applied. These findings provide a platform for these oppositely charged surfactant and polymer systems to function as stimuli-responsive or sustained-release drug delivery systems. © 2014, American Chemical Society.
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    Impact of pasteurization on the self-assembly of human milk lipids during digestion
    (Elsevier Inc on behalf of American Society for Biochemistry and Molecular Biology, 2022-05) Binte Abu Bakar, SY; Salim, M; Clulow, AJ; Hawley, A; Pelle, J; Geddes, DT; Nicholas, KR; Boyd, BJ
    Human milk is critical for the survival and development of infants. This source of nutrition contains components that protect against infections while stimulating immune maturation. In cases where the mother's own milk is unavailable, pasteurized donor milk is the preferred option. Although pasteurization has been shown to have minimal impact on the lipid and FA composition before digestion, no correlation has been made between the impact of pasteurization on the FFA composition and the self-assembly of lipids during digestion, which could act as delivery mechanisms for poorly water-soluble components. Pooled nonpasteurized and pasteurized human milk from a single donor was used in this study. The evolving FFA composition during digestion was determined using GC coupled to a flame ionization detector. In vitro digestion coupled to small-angle X-ray scattering was utilized to investigate the influence of different calcium levels, fat content, and the presence of bile salts on the extent of digestion and structural behavior of human milk lipids. Almost complete digestion was achieved when bile salts were added to the systems containing high calcium to milk fat ratio, with similar structural behavior of lipids during digestion of both types of human milk being apparent. In contrast, differences in the colloidal structures were formed during digestion in the absence of bile salt because of a greater amount of FFAs being released from the nonpasteurized than pasteurized milks. This difference in FFAs released from both types of human milk could result in varying nutritional implications for infants. © 2022 The Authors. This is an open access article under the CC BY licence
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    Impurities in commercial phytantriol significantly alter its lyotropic liquid-crystalline phase behavior
    (American Chemical Society, 2008-07-01) Dong, YD; Dong, AW; Larson, I; Rappolt, M; Amenitsch, H; Hanley, TL; Boyd, BJ
    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. © 2008, American Chemical Society
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    Liquid crystalline systems of phytantriol and glyceryl monooleate containing a hydrophilic protein: characterisation, swelling and release kinetics.
    (Wiley-Blackwell, 2009-11) Rizwan, SB; Hanley, TL; Boyd, BJ; Rades, T; Hook, S
    Swelling and phase behaviour of phytantriol and glyceryl monooleate (GMO) matrices with varying water loadings were investigated. Release of a model protein, FITC-Ova was subsequently examined. Polarised light microscopy and small angle X-ray scattering analysis showed that the addition of FITC-Ova only altered the liquid crystalline structure of phytantriol matrices at low water loadings, and that postrelease study, the phase structure of matrices at both low and high loading reflected that of the binary system. Addition of FITC-Ova to GMO matrices also altered the liquid crystalline structure when compared to the respective binary system at low but not at high loading. All samples analysed after the release study had transformed to the reverse hexagonal phase (H-II). Swelling studies revealed a faster and more extensive swelling of GMO when compared to phytantriol. Release of FITC-Ova from phytantriol matrices was faster and occurred to a greater extent most likely due to the conversion of GMO matrices into the H-II phase. No effect on release as a function of initial water content was observed for either lipid. We have confirmed that phytantriol based liquid crystalline matrices can sustain the release of a hydrophilic protein, suggesting its suitability as a potential sustained antigen-delivery system. © 2009, Wiley-Blackwell.
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    Nanostructure of liquid crystalline matrix determines in vitro sustained release and in vivo oral absorption kinetics for hydrophilic model drugs
    (Elsevier, 2009-01-05) Lee, KWY; Nguyen, TH; Hanley, TL; Boyd, BJ
    Nanostructured lipid-based liquid crystalline systems have been proposed as sustained oral drug delivery systems, but the interplay between their intrinsic release rates, susceptibility to digestive processes, and the manner in which these effects impact on their application in vivo, are not well understood. In this study, two different bicontinuous cubic phases, prepared from glyceryl monooleate and phytantriol, and a reversed hexagonal phase formed by addition of a small amount of vitamin E to phytantriol (Q(11 GMO). Q(11 PHYT) and H11 PHYT+VitEA, respectively) were prepared. The release kinetics for a number of model hydrophilic drugs with increasing molecular weights (glucose, Allura Red and FITC-clextrans) was determined in in vitro release experiments. Diffusion-controlled release was observed in all cases as anticipated from previous studies with liquid crystalline systems, and it was discovered that the release rates of each drug decreased as the matrix was changed from Q(11 GMO) to Q(11 PHYT) to H-11 PHYT VitEA. Formulations containing C-14-glucose, utilized as a rapidly absorbed marker of drug release, were then orally administered to rats to determine the relative in vivo absorption rates from the different formulations. The results showed a trend by which the rate of absorption of C-14-glucose followed that observed in the corresponding in vitro release studies, providing the first indication that the nanostructure of these materials may provide the ability to tailor the absorption kinetics of hydrophilic drugs in vivo, and hence form the basis of a new drug delivery system. © 2008, Elsevier Ltd.
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    Nonequilibrium effects in self-assembled mesophase materials: unexpected supercooling effects for cubosomes and hexosomes
    (American Chemical Society, 2010-06-01) Dong, YD; Tilley, AJ; Larson, I; Lawrence, MJ; Amenitsch, H; Rappolt, M; Hanley, TL; Boyd, BJ
    Polar lipids often exhibit equilibrium liquid crystalline structures in excess water, such as the bicontinuous cubic phases (QII) at low temperatures and inverse hexagonal phase (HII) at higher temperatures. In this study, the equilibrium and nonequilibrium phase behavior of glyceryl monooleate (GMO) and phytantriol (PHYT) systems in excess water were investigated using both continuous heating and cooling cycles, and rapid temperature changes. Evolution of the phase structure was followed using small-angle X-ray scattering (SAXS). During cooling, not only was supercooling of the liquid crystalline systems by up to 25 °C observed, but evidence for nonequilibrium phase structures (not present on heating; such as the gyroid cubic phase only present at low water content in equilibrium) was also apparent. The nonequilibrium phases were surprisingly stable, with return to equilibrium structure for dispersed submicrometer sized particle systems taking more than 13 h in some cases. Inhibition of phase nucleation was the key to greater supercooling effects observed for the dispersed particles compared to the bulk systems. These findings highlight the need for continued study into the nonequilibrium phase structures for these types of systems, as this may influence performance in applications such as drug delivery. © 2010, American Chemical Society
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    Novel spiropyran amphiphiles and their application as light-responsive liquid crystalline components
    (American Chemical Society, 2013-09-05) Tangso, KJ; Fong, WK; Darwish, TA; Kirby, N; Boyd, BJ; Hanley, TL
    Light-responsive materials formed by liquid crystalline lipids in water have potential application to drug delivery through inclusion of photochromic additives such as spiropyran. A series of novel analogues of spiropyran (SP) have been synthesized with an SP headgroup that possess a C8 (SP-OC), C12 (SP-L), and C16 (SP-P) tail to probe the influence of the length of the hydrophobic tail on their physicochemical properties and effect on behavior in liquid crystal matrices with a view to application as stimulus-responsive elements on ultraviolet irradiation. In addition, compounds possessing an oleyl (SP-OL) and phytanyl (SP-PHYT) tail, to mimic those of the ?parent? reverse bicontinuous cubic (V2) phase forming lipids, glyceryl monooleate (GMO) and phytantriol, were also prepared. The photochromic compounds were characterized by their melting points and photophysical behavior in solution using techniques including hot stage microscopy (HSM), differential scanning calorimetry (DSC), and UV?visible spectroscopy. Their effect on the equilibrium nanostructure of bulk V2 phases and phase-switching kinetics after exposure to UV light was assessed using small-angle X-ray scattering (SAXS). The melting point of the SP derivatives decreased linearly with increasing chain length, which suggests that interactions between the head groups governed their melting point, rather than the van der Waals interactions between the tails. Changing the R group did not influence the equilibrium rate constants for the isomerization of SP. Phase transition temperatures of liquid crystalline (LC) matrices were influenced significantly by incorporation of the SP derivatives and were greatest when the photochromic compound possessed an intermediate tail length substituent compared to the short alkyl or bulkier moieties. The level of disruption of lipid packing, and hence phase structure, were dependent on the duration of UV exposure. © 2013, American Chemical Society.
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    pH-responsive micelles based on caprylic acid
    (ACS Publications, 2014-06-06) Salentinig, S; Phan, S; Darwish, TA; Kirby, N; Boyd, BJ; Gilbert, EP
    Free fatty acids play a vital role as fuel for cells and in lipid metabolism. During lipid digestion in the gastrointestinal tract, triglycerides are hydrolyzed, resulting in free fatty acid and monoglyceride amphiphilic products. These components, together with bile salts, are responsible for the transport of lipids and poorly water-soluble nutrients and xenobiotics from the intestine into the circulatory system of the body. In this study, we show that the self-assembly of digestion products from medium-chain triglycerides (tricaprylin) in combination with bile salt and phospholipid is highly pH-responsive. Individual building blocks of caprylic acid within the mixed colloidal structures are mapped using a combination of small-angle X-ray and neutron scattering combined with both solvent contrast variation and selective deuteration. Modeling of the scattering data shows transitions in the size and shape of the micelles in combination with a transfer of the caprylic acid from the core of the micelles to the shell or into the bulk water upon increasing pH. The results help to understand the process of lipid digestion with a focus on colloidal structure formation and transformation for the delivery of triglyceride lipids and other hydrophobic functional molecules. © 2014, American Chemical Society.
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    Phytantriol and glyceryl monooleate cubic liquid crystalline phases as sustained-release oral drug delivery systems for poorly water soluble drugs I. Phase behaviour in physiologically-relevant media
    (Wiley-Blackwell, 2010-07) Nguyen, TH; Hanley, TL; Porter, CJH; Larson, I; Boyd, BJ
    Objectives: the potential utility of liquid crystalline lipid-based formulations in oral drug delivery is expected to depend critically on their structure formation and stability in gastrointestinal fluids. The phase behaviour of lipid-based liquid crystals formed by phytantriol and glyceryl monooleate, known to form a bicontinuous cubic phase in excess water, was therefore assessed in physiologically-relevant simulated gastrointestinal media. Methods: fixed composition phase studies, crossed polarised light microscopy (CPLM) and small angle X-ray scattering (SAXS) were used to determine the phase structures formed in phosphate-buffered saline, simulated gastric and intestinal fluids in the presence of model poorly water soluble drugs cinnarizine, diazepam and vitamin E acetate. Key findings: the phase behaviour of phytantriol in phosphate-buffered saline was very similar to that in water. Increasing concentrations of bile components (bile salts and phospholipids) caused an increase in the lattice parameter of the cubic phase structure for both lipids. Incorporation of cinnarizine and diazepam did not influence the phase behaviour of the phytantriol- or glyceryl monooleate-based systems at physiological temperatures; however, an inverse hexagonal phase formed on incorporation of vitamin E acetate. Conclusions: Phytantriol and glyceryl monooleate have the potential to form stable cubic phase liquid crystalline delivery systems in the gastrointestinal tract. In-vivo studies to assess their sustained-release behaviour are warranted. © 2010, Wiley-Blackwell.
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    Plasmonic nanorods provide reversible control over nanostructure of self-assembled drug delivery materials
    (American Chemical Society, 2010-05-04) Fong, WK; Hanley, TL; Thierry, B; Kirby, N; Boyd, BJ
    The nanostructure of mesophase liquid crystals prepared from amphiphilic lipids controls the rate of release of incorporated agents from the material, such as drug molecules, and reversible transition between different nanostructures essentially provides an “on−off” switch for release (Fong, W.-K.; Hanley, T.; Boyd, B. J. J. Controlled Release 2009, 135, 218−226). In this study, the incorporation of plasmonic hydrophobized gold nanorods (GNRs) permits reversible manipulation of nanostructure on-demand, by irradiation of the matrix using a near-infrared laser. Synchrotron small-angle X-ray scattering was used to probe the kinetics of the response of nanostructure to laser irradiation, and the specificity of the approach is shown by the lack of response in the absence of nanorods, or for GNR whose dimensions are not matched to the specific wavelength of the incident light. © 2010, American Chemical Society
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    Sensitivity of nanostructure in charged cubosomes to phase changes triggered by ionic species in solution
    (American Chemical Society, 2013-11-07) Liu, Q; Dong, YD; Hanley, TL; Boyd, BJ
    The phase behavior of dispersions comprising mixed ionic surfactant and phytantriol was precisely controlled by varying the ionic surfactant content in the mixed lipid and the ionic strength in the system. Two important trends in the phase transition of the mixed lipid systems were identified: (1) An increase in the ionic surfactant content increased the curvature of the self-assembled system toward the hydrophobic region, resulting in the phase transition from cubic phase to lamellar phase. (2) An increase in ionic strength decreased repulsion between the headgroups of the ionic surfactant, resulting in a phase transition from lamellar phase to cubic phase. The phase transitions were confirmed using small-angle X-ray scattering and cryo-TEM and were strongly correlated with the visual turbidity of the dispersions. The lipid mixture with anionic surfactant showed high sensitivity to multivalent cations for triggering the phase transition, which may be a potential strategy to develop a detection/treatment system for toxic multivalent metallic cations such as chromium. © 2013, American Chemical Society.
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    Stimuli responsive liquid crystals provide 'on-demand' drug delivery in vitro and in vivo
    (Elsevier, 2009-05-05) Fong, WK; Hanley, TL; Boyd, BJ
    Lipid-based liquid crystalline materials have been proposed as controlled drug delivery systems. Differences in liquid crystal nanostructure have previously been shown to change drug diffusion and hence release, however there has been little progress towards the use of in situ changes to nanostructure to control drug release. In this study, phytantriol and glyceryl monooleate-based bicontinuous cubic (Q(2)) and inverse hexagonal (H-2) nanostructures have been designed to allow change to the nanostructure in response to external change in temperature, with a view to controlling drug release rates in vivo. Changes to nanostructure with temperature were confirmed by crossed polarised optical microscopy and small angle X-ray scattering. Phytantriol containing 3% (w/w) vitamin E acetate provided the necessary phase transition behaviour to progress this system to in vitro release and in vivo proof of concept studies. Using glucose as a model hydrophilic drug, drug diffusion was shown to be reversible on switching between the H-2 and Q(2) nanostructures at temperatures above and below physiological temperature respectively. An in vivo proof of concept study in rats showed that after subcutaneous administration of these materials, the changes in nanostructure induced by application of a heat or cool pack at the injection site stimulated changes in drug release from the matrix anticipated from in vitro release behaviour, thereby demonstrating the potential utility of these systems as 'on demand' drug release delivery vehicles. © 2009, Elsevier Ltd.
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    Transfer of lipid between triglyceride dispersions and lyotropic liquid crystal nanostructured particles using time-resolved SAXS
    (Royal Society of Chemistry., 2012-04-16) Tilley, AJ; Dong, YD; Chong, JYT; Hanley, TL; Kirby, N; Drummond, CJ; Boyd, BJ
    Lipid-based lyotropic liquid crystalline nanostructured phases, such as the reverse bicontinuous cubic phase (V-2) and the reverse hexagonal phase (H-2), can be dispersed into submicron sized particles with often preserved internal nanostructure, termed cubosomes and hexosomes respectively. The internal nanostructure of the particles imparts desirable characteristics such as the ability to provide sustained release of active ingredients but is susceptible to change upon the incorporation of other lipids used as an active ingredient delivery system. These are complex systems in which the direction of lipid transfer, role of the stabiliser and formation of different phase structures, such as the frustrated H-2 phase are all likely to play a role but are not yet completely understood. Consequently, we have investigated the interparticle transfer of lipids between cubosomes/hexosomes and other dispersed lipids, namely triglycerides and vitamin E acetate emulsions. Time-resolved synchrotron small angle X-ray scattering was used to follow changes to nanostructure, attributed to the transfer of lipids into or out of the cubosomes. It was found that transfer of lipid occurred due to compositional ripening via a micelle-mediated mechanism, evident from the rate of lipid transfer increasing with Pluronic concentration. The rate of transfer of alkanes between liquid crystalline particles and emulsions has been shown previously to depend inversely on chain length. However in the triglyceride systems in the current study, the rate of lipid transfer (trilaurin > tricaprylin > supercooled trimyristin >> crystallised trimyristin and tristearin) did not decrease with increase in the chain length of triglyceride as might be anticipated. The equilibrium phase diagrams of triglyceride + phytantriol in excess water were determined. These diagrams showed that the transfer of phytantriol away from cubosomes to the emulsions, which increases the local triglyceride to phytantriol concentration in the cubosomes, would require formation of H-2 phase more readily for tricaprylin than for trilaurin. Therefore, the lack of correlation of transfer rate with chain length of the triglyceride was attributed to the system seeking to avoid the unfavourable formation of the H-2 phase, competing with the driving force from the entropy of mixing, and was therefore attributed as the reason for the greater rate of transfer of trilaurin compared to the less lipophilic tricaprylin. © 2012 Royal Society of Chemistry