Abstract
This review covers recent studies on the characterization of the dynamics of lipidic nanostructures formed via self-assembly processes. The focus is placed on two main topics: First, an overview of advanced experimental small-angle X-ray scattering (SAXS) setups combined with various sample manipulation techniques including, for instance, stop-flow mixing or rapid temperature-jump perturbation is given. Second, our recent synchrotron SAXS findings on the dynamic structural response of gold nanoparticle-loaded vesicles upon exposure to an ultraviolet light source, the impact of rapidly mixing negatively charged vesicles with calcium ions, and in situ hydration-induced formation of inverted-type liquid-crystalline phases loaded with the local anesthetic bupivacaine are summarized. These in situ time-resolved experiments allow real-time monitoring of the dynamics of the structural changes and the possible formation of intermediate states in the millisecond to second range. The need for investigating self-assembled systems, mainly stimuli-responsive drug nanocarriers, under nonequilibrium conditions is discussed. For pharmaceutically relevant applications, it is essential to combine these investigations with appropriate in vitro and in vivo studies.
Similar content being viewed by others
References
Ågren P, Linden M, Rosenholm JB, Schwarzenbacher R, Kriechbaum M, Amenitsch H, Laggner P, Blanchard J, Schuth F (1999) Kinetics of cosurfactant-surfactant-silicate phase behavior. 1. Short-chain alcohols. J Phys Chem B 103:5943–5948
Alam MM, Oka T, Ohta N, Yamazaki M (2011) Kinetics of low pH-induced lamellar to bicontinuous cubic phase transition in dioleoylphosphatidylserine/monoolein. J Chem Phys 134:145102
Amenitsch H, Rappolt M, Kriechbaum M, Mio H, Laggner P et al (1998) First performance assessment of the small-angle X-ray scattering beamline at ELETTRA. J Synchrotron Rad 5:506–508
Angelov B, Angelova A, Garamus VM, Lebas G, Lesieur S et al (2007) Small-angle neutron and X-ray scattering from amphiphilic stimuli-responsive diamond-type bicontinuous cubic phase. J Am Chem Soc 129:13474–13479
Angelov B, Angelova A, Vainio U, Garamus VM, Lesieur S et al (2009) Long-living intermediates during a lamellar to a diamond-cubic lipid phase transition: a small-angle X-ray scattering investigation. Langmuir 25:3734–3742
Angelov B, Angelova A, Mutafchieva R, Lesieur S, Vainio U et al (2011) SAXS investigation of a cubic to a sponge (L(3)) phase transition in self-assembled lipid nanocarriers. Phys Chem Chem Phys 13:3073–3081
Angelova A, Angelov B, Papahadjopoulos-Sternberg B, Ollivon M, Bourgaux C (2005) Proteocubosomes: nanoporous vehicles with tertiary organized fluid interfaces. Langmuir 21:4138–4143
Angelova A, Angelov B, Garamus VM, Couvreur P, Lesieur S (2012) Small-angle X-ray scattering investigations of biomolecular confinement, loading, and release from liquid-crystalline nanochannel assemblies. J Phys Chem Lett 3:445–457
Brooks NJ, Ces O, Templer RH, Seddon JM (2011) Pressure effects on lipid membrane structure and dynamics. Chem Phys Lipids 164:89–98
Caffrey M (1989) Structural, mesomorphic and time-resolved studies of biological liquid crystals and lipid membranes using synchrotron X-radiation. In: Mandelkow E (ed) Topics in Current Chemistry. Springer, Berlin, pp 75–109
Chang CM, Bodmeier R (1998) Low viscosity monoglyceride-based drug delivery systems transforming into a highly viscous cubic phase. Int J Pharm 173:51–60
Conn CE, Ces O, Mulet X, Finet S, Winter R, Seddon JM, Templer RH (2006) Dynamics of structural transformations between lamellar and inverse bicontinuous cubic lyotropic phases. Phys Rev Lett 96:108102
Couvreur P, Vauthier C (2006) Nanotechnology: intelligent design to treat complex disease. Pharm Res 23:1417–1450
de Campo L, Yaghmur A, Sagalowicz L, Leser ME, Watzke H, Glatter O (2004) Reversible phase transitions in emulsified nanostructured lipid systems. Langmuir 20:5254–5261
Deng CX, Sieling F, Pan H, Cui JM (2004) Ultrasound-induced cell membrane porosity. Ultrasound Med Biol 30:519–526
DePonte DP, Nass K, Stellato F, Liang M, Chapman HN (2011) Sample injection for pulsed x-ray sources. Proc SPIE 8078:80780M
Dong YD, Tilley AJ, Larson I, Lawrence MJ, Amenitsch H et al (2010) Nonequilibrium effects in self-assembled mesophase materials: unexpected supercooling effects for cubosomes and hexosomes. Langmuir 26:9000–9010
Fong WK, Hanley T, Boyd BJ (2009) Stimuli responsive liquid crystals provide ‘on-demand’ drug delivery in vitro and in vivo. J Control Release 135:218–226
Fong WK, Hanley TL, Thierry B, Kirby N, Boyd BJ (2010) Plasmonic nanorods provide reversible control over nanostructure of self-assembled drug delivery materials. Langmuir 26:6136–6139
Fong WK, Malic N, Evans RA, Hawley A, Boyd BJ, Hanley TL (2012) Alkylation of spiropyran moiety provides reversible photo-control over nanostructured soft materials. Biointerphases 7:3–8
Innocenzi P, Malfatti L, Kidchob T, Costacurta S, Falcaro P, Piccinini M, Marcelli A, Morini P, Sali D, Amenitsch H (2007) Time-resolved simultaneous detection of structural and chemical changes during self-assembly of mesostructured films. J Phys Chem C 111:5345–5350
Kaasgaard T, Drummond CJ (2006) Ordered 2-D and 3-D nanostructured amphiphile self-assembly materials stable in excess solvent. Phys Chem Chem Phys 8:4957–4975
Laggner P (1988) X-ray studies on biological membranes using synchrotron radiation. In: Mandelkow E (ed) Topics in Current Chemistry. Springer, Berlin, pp 173–202
Laggner P, Kriechbaum M (1991) Phospholipid phase transitions: kinetics and structural mechanisms. Chem Phys Lipids 57:121–145
Laggner P, Kriechbaum M, Rappolt M, Pabst G, Amenitsch H, Johs A, Lohner K, Zweytick D, Koschuch R, Abuja P (2005) Pharmaceutical solid-state characterization by small-and wide-angle X-ray scattering. In: Zakrzewski A, Zakrzewski M (eds) Solid State Characterization of Pharmaceuticals. Assa International, Danbury, pp 407–448
Larsson K (1989) Cubic lipid-water phases: structures and biomembrane aspects. J Phys Chem 93:7304–7314
Luzzati V (1997) Biological significance of lipid polymorphism: the cubic phases. Curr Opin Struct Biol 7:661–668
Malmsten M (2006) Soft drug delivery systems. Soft Matter 2:760–769
Malmsten M (2007) Phase transformations in self-assembly systems for drug delivery applications. J Disper Sci Technol 28:63–72
Marmiroli B, Grenci G, Cacho-Nerin F, Sartori B, Ferrari E, Laggner P, Businaro L, Amenitsch H (2009) Free jet micromixer to study fast chemical reactions by small angle X-ray scattering. Lab Chip 9:2063–2069
Moghimi SM, Peer D, Langer R (2011) Reshaping the future of nanopharmaceuticals: Ad Iudicium. ACS Nano 5:8454–8458
Mulet X, Gong X, Waddington LJ, Drummond CJ (2009) Observing self-assembled lipid nanoparticles building order and complexity through low-energy transformation processes. ACS Nano 3:2789–2797
Namiki Y, Fuchigami T, Tada N, Kawamura R, Matsunuma S, Kitamoto Y, Nakagawa M (2011) Nanomedicine for cancer: lipid-based nanostructures for drug delivery and monitoring. Accounts Chem Res 44:1080–1093
Narayanan T (2009) High brilliance small-angle X-ray scattering applied to soft matter. Curr Opin Colloid Interface Sci 14:409–415
Nguyen TH, Hanley T, Porter CJH, Larson I, Boyd BJ (2010) 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. J Pharm Pharmacol 62:844–855
Nguyen TH, Hanley T, Porter CJH, Boyd BJ (2011) Nanostructured liquid crystalline particles provide long duration sustained-release effect for a poorly water soluble drug after oral administration. J Control Rel 153:180–186
Norling T, Lading P, Engstrom S, Larsson K, Krog N, Nissen SS (1992) Formulation of a drug delivery system based on a mixture of monoglycerides and triglycerides for use in the treatment of periodontal disease. J Clin Periodontol 19:687–692
Orthen A, Wagner H, Martoiu S, Amenitsch H, Bernstorff S, Besch HJ, Menk RH, Nurdan K, Rappolt M, Walenta AH, Werthenbach U (2004) Development of a two-dimensional virtual-pixel X-ray imaging detector for time-resolved structure research. J Synchrotron Rad 11:177–186
Paasonen L, Laaksonen T, Johans C, Yliperttula M, Kontturi K, Urtti A (2007) Gold nanoparticles enable selective light-induced contents release from liposomes. J Control Rel 122:86–93
Paasonen L, Sipila T, Subrizi A, Laurinmaki P, Butcher SJ, Rappolt M, Yaghmur A, Urtti A, Yliperttula M (2010) Gold-embedded photosensitive liposomes for drug delivery: triggering mechanism and intracellular release. J Control Rel 147:136–143
Pabst G, Rappolt M, Amenitsch H, Bernstorff S, Laggner P (2000) X-ray kinematography of temperature-jump relaxation probes the elastic properties of fluid bilayers. Langmuir 16:8994–9001
Panine P, Finet S, Weiss TM, Narayanan T (2006) Probing fast kinetics in complex fluids by combined rapid mixing and small-angle X-ray scattering. Adv Colloid Interface Sci 127:9–18
Porcar L, Hamilton WA, Butler PD, Warr GG (2002) Scaling of shear-induced transformations in membrane phases. Phys Rev Lett 89:168301
Pornpattananangkul D, Olson S, Aryal S, Sartor M, Huang CM, Vecchio K, Zhang L (2010) Stimuli-responsive liposome fusion mediated by gold nanoparticles. ACS Nano 4:1935–1942
Prassl R, Pregetter M, Amenitsch H, Kriechbaum M, Schwarzenbacher R, Chapman JM, Laggner P (2008) Low density lipoproteins as circulating fast temperature sensors. PLoS ONE 3:e4079
Preiss MR, Bothun GD (2011) Stimuli-responsive liposome-nanoparticle assemblies. Exp Opin Drug Del 8:1025–1040
Rapp G, Goody RS (1991) Light as a trigger for time-resolved structural experiments on muscle, lipids, P21 and Bacteriorhodopsin. J Appl Crystallogr 24:857–865
Rappolt M, Pabst G, Rapp G, Kriechbaum M, Amenitsch H, Krenn C, Bernstorff S, Laggner P (2000) New evidence for gel-liquid crystalline phase coexistence in the ripple phase of phosphatidylcholines. Eur Biophy J 29:125–133
Rappolt M, Vidal MF, Kriechbaum M, Steinhart M, Amenitsch H, Bernstorff S, Laggner P (2003) Structural, dynamic and mechanical properties of POPC at low cholesterol concentration studied in pressure/temperature space. Eur Biophys J 31:575–585
Rappolt M, Di Gregorio GM, Almgren M, Amenitsch H, Pabst G, Laggner P, Mariani P (2006) Non-equilibrium formation of the cubic Pn3 m phase in a monoolein/water system. Europhys Lett 75:267–273
Rappolt M, Hodzic A, Sartori B, Ollivon M, Laggner P (2008) Conformational and hydrational properties during the L(beta)- to L(alpha)- and L(alpha)- to H(II)-phase transition in phosphatidylethanolamine. Chem Phys Lipids 154:46–55
Salentinig S, Sagalowicz L, Leser ME, Tedeschi C, Glatter O (2011) Transitions in the internal structure of lipid droplets during fat digestion. Soft Matter 7:650–661
Seddon AM, Lotze G, Plivelic TS, Squires AM (2011) A Highly oriented cubic phase formed by lipids under shear. J Am Chem Soc 133:13860–13863
Squires AM, Templer RH, Seddon JM, Woenkhaus J, Winter R, Narayanan T, Finet S (2005) Kinetics and mechanism of the interconversion of inverse bicontinuous cubic mesophases. Phys Rev E 72:011502
Steinhart M, Kriechbaum M, Pressl K, Amenitsch H, Laggner P, Bernstorff S (1999) High-pressure instrument for small- and wide-angle x-ray scattering. II. Time-resolved experiments. Rev Sci Instrum 70:1540–1545
Tate MW, Gruner SM (1989) Temperature-dependence of the structural dimensions of the inverted hexagonal (Hii) phase of phosphatidylethanolamine-containing membranes. Biochemistry 28:4245–4253
Teixeira CV, Amenitsch H, Linton P, Linden M, Alfredsson V (2011) The role played by salts in the formation of SBA-15, an in situ small-angle X-ray scattering/diffraction study. Langmuir 27:7121–7131
Tilley A, Dong YD, Amenitsch H, Rappolt M, Boyd BJ (2011) Transfer of lipid and phase reorganisation in self-assembled liquid crystal nanostructured particles based on phytantriol. Phys Chem Chem Phys 13:3026–3032
Toft KN, Vestergaard B, Nielsen SS, Snakenborg D, Jeppesen MG, Jacobsen JK, Arleth L, Kutter JP (2008) High-throughput small angle X-ray scattering from proteins in solution using a microfluidic front-end. Anal Chem 80:3648–3654
Vandoolaeghe P, Barauskas J, Johnsson M, Tiberg F, Nylander T (2009) Interaction between lamellar (vesicles) and nonlamellar lipid liquid-crystalline nanoparticles as studied by time-resolved small-angle X-ray diffraction. Langmuir 25:3999–4008
Warren DB, Anby MU, Hawley A, Boyd BJ (2011) Real time evolution of liquid crystalline nanostructure during the digestion of formulation lipids using synchrotron small-angle X-ray scattering. Langmuir 27:9528–9534
Weiss TM, Narayanan T, Wolf C, Gradzielski M, Panine P, Finet S, Helsby WI (2005) Dynamics of the self-assembly of unilamellar vesicles. Phys Rev Lett 94:038303
Winter R, Jeworrek C (2009) Effect of pressure on membranes. Soft Matter 5:3157–3173
Wu GH, Milkhailovsky A, Khant HA, Fu C, Chiu W, Zasadzinski JA (2008) Remotely triggered liposome release by near-infrared light absorption via hollow gold nanoshells. J Am Chem Soc 130:8175–8177
Yaghmur A, Glatter O (2009) Characterization and potential applications of nanostructured aqueous dispersions. Adv Colloid Interface Sci 147–148:333–342
Yaghmur A, Rappolt M (2011) Recent advances in the characterization of lipid-based nanocarriers. In: Garti N, Amar-Yuli I (eds) Nanotechnologies for solubilization and delivery in foods, cosmetics and pharmaceuticals. DEStech, Lancaster, pp 187–208
Yaghmur A, de Campo L, Sagalowicz L, Leser ME, Glatter O (2005) Emulsified microemulsions and oil-containing liquid crystalline phases. Langmuir 21:569–577
Yaghmur A, Laggner P, Sartori B, Rappolt M (2008) Calcium triggered Lalpha-H2 phase transition monitored by combined rapid mixing and time-resolved synchrotron SAXS. PLoS ONE 3:e2072
Yaghmur A, Kriechbaum M, Amenitsch H, Steinhart M, Laggner P, Rappolt M (2010a) Effects of pressure and temperature on the self-assembled fully hydrated nanostructures of monoolein-oil systems. Langmuir 26:1177–1185
Yaghmur A, Paasonen L, Yliperttula M, Urtti A, Rappolt M (2010b) Structural elucidation of light activated vesicles. J Phys Chem Lett 1:962–966
Yaghmur A, Larsen SW, Schmitt M, Østergaard J, Larsen C, Jensen H, Urtti A, Rappolt M (2011a) In situ characterization of lipidic bupivacaine-loaded formulations. Soft Matter 7:8291–8295
Yaghmur A, Sartori B, Rappolt M (2011b) The role of calcium in membrane condensation and spontaneous curvature variations in model lipidic systems. Phys Chem Chem Phys 13:3115–3125
Yaghmur A, Rappolt M, Østergaard J, Larsen C, Larsen SW (2012) Characterization of bupivacaine-loaded formulations based on liquid crystalline phases and microemulsions: the effect of lipid composition. Langmuir 28:2881–2889
Author information
Authors and Affiliations
Corresponding authors
Additional information
Special Issue: Scattering techniques in biology—Marking the contributions to the field from Peter Laggner on the occasion of his 68th birthday.
Rights and permissions
About this article
Cite this article
Yaghmur, A., Rappolt, M. Structural characterization of lipidic systems under nonequilibrium conditions. Eur Biophys J 41, 831–840 (2012). https://doi.org/10.1007/s00249-012-0815-7
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00249-012-0815-7