Skip to main content

Cubosomes: Structure, Preparation and Use as an Antigen Delivery System

Part of the Advances in Delivery Science and Technology book series (ADST)

Abstract

Some lipids, when dispersed in excess water can form submicron-sized particles which retain the internal microstructure of their respective parent bulk non-dispersed phase. One type of these particles possesses internally the bicontinuous cubic phase, referred to as cubosomes. Cubosomes are a versatile new drug delivery platform with potential for high loading of actives with varying physiochemical properties and the potential of sustained release. In this chapter, their application as a new platform delivery system for vaccines is reviewed, with a focus on recent data demonstrating the immunological potential of cubosomes.

Keywords

  • Major Histocompatibility Complex
  • Vaccine Delivery
  • Diacetate Succinimidyl
  • Liquid Crystalline System
  • Liquid Crystalline Dispersion

These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

This is a preview of subscription content, access via your institution.

Buying options

Chapter
USD   29.95
Price excludes VAT (USA)
  • DOI: 10.1007/978-1-4939-1417-3_7
  • Chapter length: 16 pages
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
eBook
USD   129.00
Price excludes VAT (USA)
  • ISBN: 978-1-4939-1417-3
  • Instant PDF download
  • Readable on all devices
  • Own it forever
  • Exclusive offer for individuals only
  • Tax calculation will be finalised during checkout
Softcover Book
USD   169.99
Price excludes VAT (USA)
Hardcover Book
USD   199.99
Price excludes VAT (USA)
Fig. 7.1
Fig. 7.2
Fig. 7.3
Fig. 7.4
Fig. 7.5
Fig. 7.6

References

  • Almgren M (2003) Alexander lecture 2003; cubosomes, vesicles, and perforated bilayers in aqueous systems of lipids, polymers, and surfactants. Aust J Chem 56:959–970

    CAS  CrossRef  Google Scholar 

  • Almgren M, Edwards K, Gustafsson J (1996) Cryo-transmission electron microscopy of thin vitrified samples. Curr Opin Colloid Interface Sci 1(2):270–278

    CAS  CrossRef  Google Scholar 

  • Almsherqi ZA, Kohlwein SD, Deng Y (2006) Cubic membranes: a legend beyond the Flatland of cell membrane organization. J Cell Biol 173(6):839–844. doi:10.1083/jcb.200603055

    CAS  PubMed Central  PubMed  CrossRef  Google Scholar 

  • Amar-Yuli I, Libster D, Aserin A, Garti N (2009) Solubilization of food bioactives within lyotropic liquid crystalline mesophases. Curr Opin Colloid Interface Sci 14(1):21–32. doi:10.1016/j.cocis.2008.02.001

    CAS  CrossRef  Google Scholar 

  • Andersson S, Jacob M, Lidin S, Larsson K (1995) Structure of the cubosome—a closed lipid bilayer aggregate. Z Kristallographie 210:315–318

    CAS  CrossRef  Google Scholar 

  • Barauskas J, Landh T (2003) Phase behaviour of the phytantriol/water system. Langmuir 19(23):9562–9565

    CAS  CrossRef  Google Scholar 

  • Barauskas J, Johnsson M, Joabsson F, Tiberg F (2005a) Cubic phase nanoparticles (cubosome): principles for controlling size, structure, and stability. Langmuir 21:2569–2577

    CAS  PubMed  CrossRef  Google Scholar 

  • Barauskas J, Johnsson M, Tiberg F (2005b) Self-assembled lipid superstructures: beyond vesicles and liposomes. Nano Lett 5:1615–1619

    CAS  PubMed  CrossRef  Google Scholar 

  • Bergman A, Fritz G, Glatter O (2000) Solving the generalized indirect Fourier transformation (GIFT) by Boltzmann simplex simulated annealing (BSSA). J Appl Crystallogr 33:1212–1216

    CrossRef  Google Scholar 

  • Boyd BJ, Drummond CJ, Krodkiewska I, Grieser F (2000) How chain length, headgroup polymerization, and anomeric configuration govern the thermotropic and lyotropic liquid crystalline phase behavior and the air-water interfacial adsorption of glucose-based surfactants. Langmuir 16:7359–7367

    CAS  CrossRef  Google Scholar 

  • Boyd B, Whittaker D, Khoo S, Davey G (2006) Lyotropic liquid crystalline phases formed from glycerate surfactants as sustained release drug delivery systems. Int J Pharm 309:216–226

    CrossRef  Google Scholar 

  • Boyd BJ, Rizwan SB, Dong Y, Hook S, Rades T (2007) Self-assembled geometric liquid-crystalline nanoparticles imaged in three dimensions: hexosomes are not necessarily flat hexagonal prisms. Langmuir 23(25):12461–12464

    CAS  PubMed  CrossRef  Google Scholar 

  • Caffrey M (2000) A lipid’s eye view of membrane protein crystallization in mesophases. Curr Opin Struct Biol 10(4):486–497. doi:10.1016/S0959-440X(00)00119-6

    CAS  PubMed  CrossRef  Google Scholar 

  • Chang C, Bodmeier R (1997) Swelling of and drug release from monoglyceride-based drug delivery systems. J Pharm Sci 86(6):747–752

    CAS  PubMed  CrossRef  Google Scholar 

  • Cherezov V, Clogston J, Papiz MZ, Caffrey M (2006) Room to move: crystallizing membrane proteins in swollen lipidic mesophases. J Mol Biol 357(5):1605–1618. doi:10.1016/j.jmb.2006.01.049

    CAS  PubMed  CrossRef  Google Scholar 

  • Chong JYT, Mulet X, Waddington LJ, Boyd BJ, Drummond CJ (2011) Steric stabilisation of self-assembled cubic lyotropic liquid crystalline nanoparticles: high throughput evaluation of triblock polyethylene oxide-polypropylene oxide-polyethylene oxide copolymers. Soft Matter 7(10):4768–4777. doi:10.1039/C1SM05181D

    CAS  CrossRef  Google Scholar 

  • Chung H, Kim J, Kwon I, Jeong S (2002) Self-assembled “nanocubicle” as a carrier for peroral insulin delivery. Diabetologica 45:448–451

    CAS  CrossRef  Google Scholar 

  • Clogston J, Caffrey M (2005) Controlling release from the lipidic cubic phase. Amino acids, peptides, proteins and nucleic acid. J Control Release 107:97–111

    CAS  PubMed  CrossRef  Google Scholar 

  • Colotto A, Epand RM (1997) Structural study of the relationship between the rate of membrane fusion and the ability of the fusion peptide of influenza virus to perturb bilayers. Biochemistry 36(25):7644–7651. doi:10.1021/bi970382u

    CAS  PubMed  CrossRef  Google Scholar 

  • Cools N, Ponsaerts P, Van Tendeloo VFI, Berneman ZN (2007) Balancing between immunity and tolerance: an interplay between dendritic cells, regulatory T cells, and effector T cells. J Leukoc Biol 82:1365–1374

    CAS  PubMed  CrossRef  Google Scholar 

  • Dan Y, Poo M-M (2004) Spike timing-dependent plasticity of neural circuits. Neuron 44(1):23–30

    CAS  PubMed  CrossRef  Google Scholar 

  • Deng Y, Kohlwein SD, Mannella CA (2002) Fasting induces cyanide-resistant respiration and oxidative stress in the amoeba Chaos carolinensis: implications for the cubic structural transition in mitochondrial membranes. Protoplasma 219(3–4):160–167. doi:10.1007/s007090200017

    CAS  PubMed  CrossRef  Google Scholar 

  • Dong Y, Larson I, Hanley T, Boyd BJ (2006) Bulk and dispersed aqueous phase behavior of phytantriol: effect of vitamin E acetate and F127 polymer on liquid crystal structure. Langmuir 22:9512–9518

    CAS  PubMed  CrossRef  Google Scholar 

  • Fong C, Wells D, Krodkiewska I, Booth J, Hartley PJ (2007) Synthesis and mesophases of glycerate surfactants. J Phys Chem B 111:1384–1392

    CAS  PubMed  CrossRef  Google Scholar 

  • Gabizon A, Shmeeda H, Horowitz AT, Zalipsky S (2004) Tumor cell targeting of liposome-entrapped drugs with phospholipid-anchored folic acid-PEG conjugates. Adv Drug Deliv Rev 56:1177–1192

    CAS  PubMed  CrossRef  Google Scholar 

  • Ganem-Quintanar A, Quintanar-Guerrero D, Buri P (2000) Monoolein: a review of the pharmaceutical applications. Drug Dev Ind Pharm 26(8):809–820

    CAS  PubMed  CrossRef  Google Scholar 

  • Garti N, Libster D, Aserin A (2012) Lipid polymorphism in lyotropic liquid crystals for triggered release of bioactives. Food Funct 3(7):700–713

    CAS  PubMed  CrossRef  Google Scholar 

  • Gregoriadis G (1990) Immunological adjuvants: a role for liposomes. Immunol Today 11:89–97. doi:10.1016/0167-5699(90)90034-7

    CAS  PubMed  CrossRef  Google Scholar 

  • Guo C, Wang J, Cao F, Lee RJ, Zhai G (2010) Lyotropic liquid crystal systems in drug delivery. Drug Discov Today 15(23–24):1032–1040. doi:10.1016/j.drudis.2010.09.006

    CAS  PubMed  CrossRef  Google Scholar 

  • Gustafsson J, Ljusberg-Wahren H, Almgren M, Larsson K (1997) Submicron particles of reversed lipid phases in water stabilized by a nonionic amphiphilic polymer. Langmuir 13:6964–6971

    CAS  CrossRef  Google Scholar 

  • Hato M, Minamikawa H (1996) The effects of oligo saccharide stereochemistry on the physical properties of aqueous synthetic lipids. Langmuir 12:1658–1665

    CAS  CrossRef  Google Scholar 

  • Hyde S (2001) Identification of lyotropic liquid crystal mesophases, Chap 16. In: Holmberg K (ed) Handbook of applied surface and colloid chemistry. Wiley, New York, pp 299–331

    Google Scholar 

  • Israelachvili JN, Mitchell DJ, Ninham BW (1976) Theory of self-assembly of hydrocarbon amphiphiles into micelles and bilayers. J Chem Soc Faraday Trans 2 72:1525–1568

    CrossRef  Google Scholar 

  • 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

    CAS  PubMed  CrossRef  Google Scholar 

  • Kaisho T, Akira S (2002) Toll-like receptors as adjuvant receptors. Biochim Biophys Acta 1589:1–13

    CAS  PubMed  CrossRef  Google Scholar 

  • Krauel K, Girvan L, Hook S, Rades T (2007) Characterisation of colloidal drug delivery systems from the naked eye to Cryo-FESEM. Micron 38:796–803

    CAS  PubMed  CrossRef  Google Scholar 

  • Lara MG, Bentley MV, Collet JH (2005) In vitro drug release mechanism and drug loading studies of cubic phase gels. Int J Pharm 293:241–250

    CAS  PubMed  CrossRef  Google Scholar 

  • Larsson K (1983) Two cubic phases in monoolein-water system. Nature 304(5927):664

    CrossRef  Google Scholar 

  • Larsson K (1989) Cubic lipid-water phases: structures and biomembrane aspects. J Phys Chem 93:7304–7314

    CAS  CrossRef  Google Scholar 

  • Larsson K (1999) Colloidal dispersions of ordered lipid-water phases. J Dispers Sci Technol 20:27–34

    CAS  CrossRef  Google Scholar 

  • Larsson K (2000) Aqueous dispersions of cubic lipid-water phases. Curr Opin Colloid Interface Sci 5:64–69

    CAS  CrossRef  Google Scholar 

  • Lee HK, Iwasaki A (2007) Innate control of adaptive immunity: dendritic cells and beyond. Semin Immunol 19:48–55

    CAS  PubMed  CrossRef  Google Scholar 

  • Lindblom G, Rilfors L (1989) Cubic phases and isotropic structures formed by membrane lipids—possible biological relevance. Biochim Biophys Acta 988:221–256

    CAS  CrossRef  Google Scholar 

  • Luzzati V (1997) Biological significance of lipid polymorphism: the cubic phases. Curr Opin Struct Biol 7:661–668

    CAS  PubMed  CrossRef  Google Scholar 

  • Mulet X, Boyd BJ, Drummond CJ (2013) Advances in drug delivery and medical imaging using colloidal lyotropic liquid crystalline dispersions. J Colloid Interface Sci 393:1–20. doi:10.1016/j.jcis.2012.10.014

    CAS  PubMed  CrossRef  Google Scholar 

  • Myschik J, Rades T, Hook S (2009) Advances in lipid-based subunit vaccine formulations. Curr Immunol Rev 5:42–48

    CAS  CrossRef  Google Scholar 

  • Nakano M, Sugita A, Matsuoka H, Handa T (2001) Small-angle x-ray scattering and 13C NMR investigation on the internal structure of “cubosomes”. Langmuir 17(13):3917–3922

    CAS  CrossRef  Google Scholar 

  • Nakano M, Teshigawara T, Sugita A, Leesajakul W, Taniguchi A, Kamo T, Matsuoka H, Handa T (2002) Dispersions of liquid crystalline phases of the monoolein/oleic acid/pluronic F127 system. Langmuir 18:9283–9288

    CAS  CrossRef  Google Scholar 

  • Patton JS, Carey MC (1979) Watching fat digestion. Science 204(4389):145

    CAS  PubMed  CrossRef  Google Scholar 

  • Pawley J (1997) The development of field-emission scanning electron microscopy for imaging biological surfaces. Scanning 19:324–336

    CAS  PubMed  Google Scholar 

  • Pratt L (1985) Theory of hydrophobic effects. Annu Rev Phys Chem 36:433–449

    CAS  CrossRef  Google Scholar 

  • Quantan N, Spicer J, Plunkett T, Pandha H (2004) Cellular immunotherapy for cancer: current concepts and clinical perspectives scientific basis and approaches for therapeutic cancer vaccines: Part 1. Clin Oncol 16:356–365

    CrossRef  Google Scholar 

  • Rattanapak T, Young K, Rades T, Hook S (2012) Comparative study of liposomes, transfersomes, ethosomes and cubosomes for transcutaneous immunisation: characterisation and in vitro skin penetration. J Pharm Pharmacol 64(11):1560–1569. doi:10.1111/j.2042-7158.2012.01535.x

    CAS  PubMed  CrossRef  Google Scholar 

  • Rattanapak T, Birchall J, Young K, Ishii M, Meglinski I, Rades T, Hook S (2013) Transcutaneous immunization using microneedles and cubosomes: mechanistic investigations using optical coherence tomography and two-photon microscopy. J Control Release 172(3):894–903. doi:10.1016/j.jconrel.2013.08.018

    CAS  PubMed  CrossRef  Google Scholar 

  • Ribier A, Biatry B (1998) Cosmetic or dermatological composition in the form of an aqueous and stable dispersion of cubic gel particles based on phytanetriol and containing a surface-active agent which has a fatty chain, as dispersing and stabilizing agent. US Patent

    Google Scholar 

  • Rizwan SB, Dong Y, Boyd BJ, Rades T, Hook S (2007) Characterisation of bicontinuous cubic liquid crystalline systems of phytantriol and water using cryo field emission scanning electron microscopy (cryo FESEM). Micron 38(5):478–485

    CAS  PubMed  CrossRef  Google Scholar 

  • Rizwan SB, Hanley T, Boyd BJ, Hook S (2009) Liquid crystalline systems of phytantriol and glyceryl monooleate containing a hydrophilic protein: characterisation, swelling and release kinetics. J Pharm Sci 98(11):4191–4204

    CAS  PubMed  CrossRef  Google Scholar 

  • Rizwan SB, Boyd BJ, Rades T, Hook S (2010) Bicontinuous cubic liquid crystals as sustained delivery systems for peptides and proteins. Expert Opin Drug Deliv 7(10):1133–1144

    CAS  PubMed  CrossRef  Google Scholar 

  • Rizwan SB, Assmus D, Boehnke A, Hanley T, Boyd BJ, Rades T, Hook S (2011) Preparation of phytantriol cubosomes by solvent precursor dilution for the delivery of protein vaccines. Eur J Pharm Biopharm 79(1):15–22. doi:10.1016/j.ejpb.2010.12.034

    CAS  PubMed  CrossRef  Google Scholar 

  • Rizwan SB, McBurney WT, Young K, Hanley T, Boyd BJ, Rades T, Hook S (2013) Cubosomes containing the adjuvants imiquimod and monophosphoryl lipid A stimulate robust cellular and humoral immune responses. J Control Release 165(1):16–21. doi:10.1016/j.jconrel.2012.10.020

    CAS  PubMed  CrossRef  Google Scholar 

  • Schlosser E, Mueller M, Fischer S, Basta S, Busch DH, Gander B, Groettrup M (2008) TLR ligands and antigen need to be coencapsulated into the same biodegradable microsphere for the generation of potent cytotoxic T lymphocyte responses. Vaccine 26:1626–1637

    CAS  PubMed  CrossRef  Google Scholar 

  • Seddon JM, Templer RH (1993) Cubic phases of self-assembled amphiphilic aggregates. Philos Trans R Soc Lond A 344(1672):377–401

    CAS  CrossRef  Google Scholar 

  • Shearman GC, Templer RH, Seddon JM (2006) Inverse lyotropic phases of lipids and membrane curvature. J Phys Condens Matter 18:S1105–S1124

    CAS  PubMed  CrossRef  Google Scholar 

  • Spicer P, Hayden K, Lynch ML, Ofori-Boateng A, Burns JL (2001) Novel process for producing cubic liquid crystalline nanoparticles (cubosomes). Langmuir 17(19):5748–5756

    CAS  CrossRef  Google Scholar 

  • Spicer P, Small WB II, Lynch ML, Burns JL (2002) Dry powder precursors of cubic liquid crystalline nanoparticles (cubosome). J Nanopart Res 4:297–311

    CAS  CrossRef  Google Scholar 

  • Tilley AJ, Drummond CJ, Boyd BJ (2013) Disposition and association of the steric stabilizer Pluronic® F127 in lyotropic liquid crystalline nanostructured particle dispersions. J Colloid Interface Sci 392:288–296. doi:10.1016/j.jcis.2012.09.051

    CAS  PubMed  CrossRef  Google Scholar 

  • van Duikeren S, Fransen MF, Redeker A, Wieles B, Platenburg G, Krebber W-J, Ossendorp F, Melief CJM, Arens R (2012) Vaccine-induced effector-memory CD8+ T cell responses predict therapeutic efficacy against tumors. J Immunol 189(7):3397–3403. doi:10.4049/jimmunol.1201540

    PubMed  CrossRef  Google Scholar 

  • Wörle G, Siekmann B, Bunjes H (2006a) Effect of drug loading on the transformation of vesicular into cubic nanoparticles during heat treatment of aqueous monoolein/poloxamer dispersions. Eur J Pharm Biopharm 63:128–133

    PubMed  CrossRef  Google Scholar 

  • Wörle G, Siekmann B, Koch M, Bunjes H (2006b) Transformation of vesicular into cubic nanoparticles by autoclaving of aqueous monoolein/poloxamer dispersions. Eur J Pharm Sci 27:44–53

    PubMed  CrossRef  Google Scholar 

  • Yaghmur A, Glatter O (2008) Characterization and potential applications of nanostructured aqueous dispersions. Adv Colloid Interface Sci 147–148:333–342

    PubMed  Google Scholar 

  • Yano A, Onouka A, Asahi-Ozaki Y, Imai S, Hanada N, Miwa Y, Nisizawa T (2005) An ingenious design for peptide vaccines. Vaccine 23:2322–2326

    CAS  PubMed  CrossRef  Google Scholar 

  • Zheng L, Um J, Chung H, Kwon I, Li G, Jeong S (2003) Microstructure of dispersed colloidal particles of a bilayer cubic phase. J Dispers Sci Technol 24(1):123–128

    CAS  CrossRef  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Shakila B. Rizwan .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and Permissions

Copyright information

© 2015 Springer Science+Business Media New York

About this chapter

Cite this chapter

Rizwan, S.B., Boyd, B.J. (2015). Cubosomes: Structure, Preparation and Use as an Antigen Delivery System. In: Foged, C., Rades, T., Perrie, Y., Hook, S. (eds) Subunit Vaccine Delivery. Advances in Delivery Science and Technology. Springer, New York, NY. https://doi.org/10.1007/978-1-4939-1417-3_7

Download citation