Abstract
Bilayer vesicles can be prepared from a range of molecules including nonionic surfactants. Vesicles built from nonionic surfactants are known as nonionic surfactant vesicles or niosomes. Whilst structurally similar to liposomes, the use of nonionic surfactants in a formulation may offer advantages in terms of chemical stability and reduced cost in some cases. In general, the ability of surfactant blends to form vesicles is dependent on their combined critical packing parameter, with cholesterol often being used to support the formation of vesicle constructs. To enhance the potency and delivery of antigens, niosomes can be designed to protect antigens against degradation in harsh in vivo environments, including the oral route, and enhance delivery of antigens to appropriate target sites. Key considerations in the design of niosomal adjuvants include the choice of surfactants, the surface properties of the vesicles, the method of preparation, the cholesterol content and the inclusion of immunostimulatory agents. Manipulation of these attributes allows vesicle constructs to be designed and built that can be used to deliver antigens via a range of delivery routes.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Similar content being viewed by others
References
Ali MH, Kirby DJ, Mohammed AR, Perrie Y (2010) Solubilisation of drugs within liposomal bilayers: alternatives to cholesterol as a membrane stabilising agent. J Pharm Pharmacol 62(11):1646–1655
Allen TM, Hansen CB, de Menezes DEL (1995) Pharmacokinetics of long-circulating liposomes. Adv Drug Deliv Rev 16(2–3):267–284
Almeida J, Edwards DC, Brand C, Heath T (1975) Formation of virosomes from influenza subunits and liposomes. Lancet 306(7941):899–901
Arunothayanun P, Uchegbu IF, Craig DQM, Turton JA, Florence AT (1999) In vitro/in vivo characterisation of polyhedral niosomes. Int J Pharm 183(1):57–61
Azmin MN, Florence AT, Handjani-Vila RM, Stuart JF, Vanlerberghe G, Whittaker JS (1985) The effect of non-ionic surfactant vesicle (niosome) entrapment on the absorption and distribution of methotrexate in mice. J Pharm Pharmacol 37(4):237–242
Baillie AJ, Florence AT, Hume LR, Muirhead GT, Rogerson A (1985) The preparation and properties of niosomes—non-ionic surfactant vesicles. J Pharm Pharmacol 37(12):863–868
Bangham AD, Horne RW (1964) Negative staining of phospholipids and their structural modification by surface-active agents as observed in the electron microscope. J Mol Biol 8(5):660-668
Barakat HS, Darwish IA, El-Khordagui LK, Khalafallah NM (2009) Development of naftifine hydrochloride alcohol-free niosome gel. Drug Dev Ind Pharm 35(5):631–637
Barenholzt Y, Amselem S, Lichtenberg D (1979) A new method for preparation of phospholipid vesicles (liposomes)—French press. FEBS Lett 99(1):210–214
Batzri S, Korn ED (1973) Single bilayer liposomes prepared without sonication. Biochim Biophys Acta 298(4):1015–1019
Bayindir ZS, Yuksel N (2010) Characterization of niosomes prepared with various nonionic surfactants for paclitaxel oral delivery. J Pharm Sci 99(4):2049–2060
Bennett E, Mullen AB, Ferro VA (2009) Translational modifications to improve vaccine efficacy in an oral influenza vaccine. Methods 49(4):322–327
Bibi S, Kaur R, Henriksen-Lacey M, McNeil SE, Wilkhu J, Lattmann E, Christensen D, Mohammed AR, Perrie Y (2011) Microscopy imaging of liposomes: from coverslips to environmental SEM. Int J Pharm 417(1–2):138–150
Biswal S, Murthy PN, Sahu J, Sahoo P, Amir F (2008) Vesicles of non-ionic surfactants (niosomes) and drug delivery potential. Int J Pharm Sci Nanotechnol 1(1):1–8
Bramwell VW, Perrie Y (2005) The rational design of vaccines. Drug Discov Today 10(22):1527–1534
Brewer JM, Alexander J (1992) The adjuvant activity of non-ionic surfactant vesicles (niosomes) on the BALB/c humoral response to bovine serum albumin. Immunology 75(4):570–575
Brewer JM, Alexander J (1994) Studies on the adjuvant activity of non-ionic surfactant vesicles: adjuvant-driven IgG2a production independent of MHC control. Vaccine 12(7):613–619
Brewer JM, Conacher M, Satoskar A, Bluethmann H, Alexander J (1996) In interleukin-4-deficient mice, alum not only generates T helper 1 responses equivalent to Freund’s complete adjuvant, but continues to induce T helper 2 cytokine production. Eur J Immunol 26(9):2062–2066
Brewer JM, Roberts CW, Stimson WH, Alexander J (1995) Accurate determination of adjuvant-associated protein or peptide by ninhydrin assay. Vaccine 13(15):1441–1444
Carafa M, Santucci E, Alhaique F, Coviello T, Murtas E, Riccieri FM, Lucania G, Torrisi MR (1998) Preparation and properties of new unilamellar non-ionic/ionic surfactant vesicles. Int J Pharm 160(1):51–59
Chambers MA, Wright DC, Brisker J, Williams A, Hatch G, Gavier-Widen D, Hall G, Marsh PD, Glyn Hewinson R (2004) A single dose of killed Mycobacterium bovis BCG in a novel class of adjuvant (Novasome) protects guinea pigs from lethal tuberculosis. Vaccine 22(8):1063–1071
Conacher M, Alexander J, Brewer JM (2001) Oral immunisation with peptide and protein antigens by formulation in lipid vesicles incorporating bile salts (bilosomes). Vaccine 19(20–22):2965–2974
Corr SC, Gahan CCGM, Hill C (2008) M-cells: origin, morphology and role in mucosal immunity and microbial pathogenesis. FEMS Immunol Med Microbiol 52(1):2–12
Davidsen J, Rosenkrands I, Christensen D, Vangala A, Kirby D, Perrie Y, Agger EM, Andersen P (2005) Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6′-dibehenate)—a novel adjuvant inducing both strong CMI and antibody responses. Biochim Biophys Acta 1718(1–2):22–31
Deamer D, Bangham AD (1976) Large volume liposomes by an ether vaporization method. Biochim Biophys Acta 443(3):629–634
Desjardins R, Krzystyniak K, Thérien H-M, Banska W, Tancrede P, Fournier M (1995) Immunoactivating potential of multilamellar liposome vesicles (MLV) in murine popliteal lymph node (PLN) test. Int J Immunopharmacol 17(5):367–374
Devaraj GN, Parakh SR, Devraj R, Apte SS, Rao BR, Rambhau D (2002) Release studies on niosomes containing fatty alcohols as bilayer stabilizers instead of cholesterol. J Colloid Interface Sci 251(2):360–365
Eldridge JH, Hammond CJ, Meulbroek JA, Staas JK, Gilley RM, Tice TR (1990) Controlled vaccine release in the gut-associated lymphoid tissues. I. Orally administered biodegradable microspheres target the peyer’s patches. J Control Release 11(1–3):205–214
Felgner PL, Gadek TR, Holm M, Roman R, Chan HW, Wenz M, Northrop JP, Ringold GM, Danielsen M (1987) Lipofection: a highly efficient, lipid-mediated DNA-transfection procedure. Proc Natl Acad Sci U S A 84(21):7413–7417
Freitas C, Müller RH (1998) Effect of light and temperature on zeta potential and physical stability in solid lipid nanoparticle (SLN™) dispersions. Int J Pharm 168(2):221–229
González-RodrÃguez M, Rabasco A (2011) Charged liposomes as carriers to enhance the permeation through the skin. Expert Opin Drug Deliv 8(7):857–871
Gregoriadis G (1990) Immunological adjuvants: a role for liposomes. Immunology Today 11:89–97
Gregoriadis G, Leathwood PD, et al (1971) Enzyme entrapment in liposomes. FEBS Letters 14(2):95–99
Guinedi AS, Mortada ND, Mansour S, Hathout RM (2005) Preparation and evaluation of reverse-phase evaporation and multilamellar niosomes as ophthalmic carriers of acetazolamide. Int J Pharm 306(1–2):71–82
Gupta PN, Mishra V, Rawat A, Dubey P, Mahor S, Jain S, Chatterji DP, Vyas SP (2005) Non-invasive vaccine delivery in transfersomes, niosomes and liposomes: a comparative study. Int J Pharm 293(1–2):73–82
Handjani-Vila RM, Ribier A, Rondot B, Vanlerberghie G (1979) Dispersions of lamellar phases of non-ionic lipids in cosmetic products. Int J Cosmet Sci 1(5):303–314
Hong M, Zhu S, Jiang Y, Tang G, Pei Y (2009) Efficient tumor targeting of hydroxycamptothecin loaded PEGylated niosomes modified with transferrin. J Control Release 133(2):96–102
Hood E, Gonzalez M, Plaas A, Strom J, VanAuker M (2007) Immuno-targeting of nonionic surfactant vesicles to inflammation. Int J Pharm 339(1–2):222–230
Huang Y-Z, Gao J-Q, Chen J-L, Liang W-Q (2006) Cationic liposomes modified with non-ionic surfactants as effective non-viral carrier for gene transfer. Colloids Surf B Biointerfaces 49(2):158–164
Israelachvili JN, Mitchell DJ (1975) A model for the packing of lipids in bilayer membranes. Biochim Biophys Acta 389(1):13–19
Israelachvili JN, Mitchell DJ, Ninham BW (1977) Theory of self-assembly of lipid bilayers and vesicles. Biochim Biophys Acta 470(2):185–201
Jadon P, Gajbhiye V, Jadon R, Gajbhiye K, Ganesh N (2009) Enhanced oral bioavailability of griseofulvin via niosomes. AAPS PharmSciTech 10(4):1186–1192
Jain S, Singh P, Mishra V, Vyas SP (2005) Mannosylated niosomes as adjuvant-carrier system for oral genetic immunization against Hepatitis B. Immunol Lett 101(1):41–49
Kensil CR (1996) Saponins as vaccine adjuvants. Crit Rev Ther Drug Carrier Syst 13(1–2):1–55
Kirby C, Gregoriadis G (1984) Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes. Nat Biotechnol 2(11):979–984
Konnings S, Copland MJ, Davies NM, Rades T (2002) A method for the incorporation of ovalbumin into immune stimulating complexes prepared by the hydration method. Int J Pharm 241(2):385–389
Kruger NJ (2002) The Bradford method for protein quantitation. In: Walker JM (ed) The protein protocols handbook. Humana Press, Totowa, pp 15–21
Kumar VV (1991) Complementary molecular shapes and additivity of the packing parameter of lipids. Proc Natl Acad Sci U S A 88(2):444–448
Lasic DD (1990) On the thermodynamic stability of liposomes. J Colloid Interface Sci 140(1):302–304
Lasic DD, Martin FJ, Gabizon A, Huang SK, Papahadjopoulos D (1991) Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim Biophys Acta 1070(1):187–192
Lendemans DG, Egert AM, Hook S, Rades T (2007) Cage-like complexes formed by DOTAP, Quil-A and cholesterol. Int J Pharm 332(1–2):192–195
Lendemans DG, Myschik J, Hook S, Rades T (2005) Cationic cage-like complexes formed by DC-cholesterol, Quil-A, and phospholipid. J Pharm Sci 94(8):1794–1807
Lowry OH, Rosebrough NJ, Farr AL, Randall RJ (1951) Protein measurement with the folin phenol reagent. J Biol Chem 193(1):265–275
Mann JFS, Ferro VA, Mullen AB, Tetley L, Mullen M, Carter KC, Alexander J, Stimson WH (2004) Optimisation of a lipid based oral delivery system containing A/Panama influenza haemagglutinin. Vaccine 22(19):2425–2429
Mann JFS, Scales HE, Shakir E, Alexander J, Carter KC, Mullen AB, Ferro VA (2006) Oral delivery of tetanus toxoid using vesicles containing bile salts (bilosomes) induces significant systemic and mucosal immunity. Methods 38(2):90–95
Mann JFS, Shakir E, Carter KC, Mullen AB, Alexander J, Ferro VA (2009) Lipid vesicle size of an oral influenza vaccine delivery vehicle influences the Th1/Th2 bias in the immune response and protection against infection. Vaccine 27(27):3643–3649
Manosroi A, Khanrin P, Lohcharoenkal W, Werner RG, Götz F, Manosroi W, Manosroi J (2010) Transdermal absorption enhancement through rat skin of gallidermin loaded in niosomes. Int J Pharm 392(1–2):304–310
Manosroi A, Wongtrakul P, Manosroi J, Sakai H, Sugawara F, Yuasa M, Abe M (2003) Characterization of vesicles prepared with various non-ionic surfactants mixed with cholesterol. Colloids Surf B Biointerfaces 30(1–2):129–138
Moghaddam B, Ali MH, Wilkhu J, Kirby DJ, Mohammed AR, Zheng Q, Perrie Y (2011) The application of monolayer studies in the understanding of liposomal formulations. Int J Pharm 417(1–2):235–244
Mohammed AR, Bramwell VW, Coombes AGA, Perrie Y (2006) Lyophilisation and sterilisation of liposomal vaccines to produce stable and sterile products. Methods 40(1):30–38
Mohammed AR, Bramwell VW, Kirby DJ, McNeil SE, Perrie Y (2010) Increased potential of a cationic liposome-based delivery system: enhancing stability and sustained immunological activity in pre-clinical development. Eur J Pharm Biopharm 76(3):404–412
Mokhtar M, Sammour OA, Hammad MA, Megrab NA (2008) Effect of some formulation parameters on flurbiprofen encapsulation and release rates of niosomes prepared from proniosomes. Int J Pharm 361(1–2):104–111
Mowat MA (2003) Anatomical basis of tolerance and immunity to intestinal antigens. Nature 3:331–341
Murdan S, Gregoriadis G, Florence AT (1999) Sorbitan monostearate/polysorbate 20 organogels containing niosomes: a delivery vehicle for antigens? Eur J Pharm Sci 8(3):177–185
New R (1990) Liposomes a practical approach. Oxford University Press, New York, pp 1–32
Ning M, Guo Y, Pan H, Yu H, Gu Z (2005) Niosomes with sorbitan monoester as a carrier for vaginal delivery of insulin: studies in rats. Drug Deliv 12(6):399–407
Norris DA, Puri N, Sinko PJ (1998) The effect of physical barriers and properties on the oral absorption of particulates. Adv Drug Deliv Rev 34(2–3):135–154
Obrenovic MM, Perrie Y, Gregoriadis G (1998) Entrapment of plasmid DNA into niosomes: characterization studies. J Pharm Pharmacol 50(S9):155
Okada JI, Cohen S, Langer R (1995) In vitro evaluation of polymerized liposomes as an oral drug delivery system. Pharm Res 12(4):576–582
Papahadjopoulos D, Vail WJ, Jacobson K, Poste G (1975) Cochleate lipid cylinders: formation by fusion of unilamellar lipid vesicles. Biochim Biophys Acta 394(3):483–491
Perrie Y, Barralet JE, McNeil S, Vangala A (2004) Surfactant vesicle-mediated delivery of DNA vaccines via the subcutaneous route. Int J Pharm 284(1–2):31–41
Perrie Y, Obrenovic M, McCarthy D, Gregoriadis G (2002) Liposome (Lipodine™)-mediated DNA vaccination by the oral route. J Liposome Res 12(1–2):185–197
Perrie Y, Rades T (2012) FASTtrack: pharmaceutics—drug delivery and targeting. 2nd edn. Pharmaceutical Press, London
Rentel CO, Bouwstra JA, Naisbett B, Junginger HE (1999) Niosomes as a novel peroral vaccine delivery system. Int J Pharm 186(2):161–167
Sasaki S, Takeshita F, Xin K-Q, Ishii N, Okuda K (2003) Adjuvant formulations and delivery systems for DNA vaccines. Methods 31(3):243–254
Schubert R, Jaroni H, Schoelmerich J, Schmidt KH (1983) Studies on the mechanism of bile salt-induced liposomal membrane damage. Digestion 28(3):181–190
Shakweh M, Besnard M, Nicolas V, Fattal E (2005) Poly (lactide-co-glycolide) particles of different physicochemical properties and their uptake by peyer’s patches in mice. Eur J Pharm Biopharm 61:1–13
Shukla A, Katare OP, Singh B, Vyas SP (2010) M-cell targeted delivery of recombinant hepatitis B surface antigen using cholera toxin B subunit conjugated bilosomes. Int J Pharm 385(1–2):47–52
Srinivas S, Kumar YA, Hemanth A, Anitha M (2010) Preparation and evaluation of niosomes containing aceclofenac. Digest J Nanomater Biostruct 5(1):249–254
Szoka F, Papahadjopoulos D (1978) Procedure for preparation of liposomes with large internal aqueous space and high capture by reverse-phase evaporation. Proc Natl Acad Sci U S A 75(9):4194–4198
Szoka F, Papahadjopoulos D (1980) Comparative properties and methods of preparation of lipid vesicles (liposomes). Annu Rev Biophys Bioeng 9(1):467–508
Tabata Y, Ikada Y (1988) Effect of the size and surface charge of polymer microspheres on their phagocytosis by macrophage. Biomaterials 9(4):356–362
Taylor KMG, Morris RM (1995) Thermal analysis of phase transition behaviour in liposomes. Thermochim Acta 248:289–301
Uchegbu IF, Double JA, Turton JA, Florence AT (1995) Distribution, metabolism and tumoricidal activity of doxorubicin administered in sorbitan monostearate (Span 60) niosomes in the mouse. Pharm Res 12(7):1019–1024
Uchegbu IF, Duncan R (1997) Niosomes containing N-(2-hydroxypropyl)methacrylamide copolymer-doxorubicin (PK1): effect of method of preparation and choice of surfactant on niosome characteristics and a preliminary study of body distribution. Int J Pharm 155(1):7–17
Uchegbu IF, Florence AT (1995) Non-ionic surfactant vesicles (niosomes): physical and pharmaceutical chemistry. Adv Colloid Interface Sci 58(1):1–55
Uchegbu IF, Vyas SP (1998) Non-ionic surfactant based vesicles (niosomes) in drug delivery. Int J Pharm 172(1–2):33–70
van Hal DA, Bouwstra JA, van Rensen A, Jeremiasse E, de Vringer T, Junginger HE (1996) Preparation and characterization of nonionic surfactant vesicles. J Colloid Interface Sci 178(1):263–273
Vangala A, Bramwell VW, McNeil S, Christensen D, Agger EM, Perrie Y (2007) Comparison of vesicle based antigen delivery systems for delivery of hepatitis B surface antigen. J Control Release 119(1):102–110
Vangala A, Kirby D, Rosenkrands I, Agger EM, Andersen P, Perrie Y (2006) A comparative study of cationic liposome and niosome-based adjuvant systems for protein subunit vaccines: characterisation, environmental scanning electron microscopy and immunisation studies in mice. J Pharm Pharmacol 58(6):787–799
Vyas SP, Singh RP, Jain S, Mishra V, Mahor S, Singh P, Gupta PN, Rawat A, Dubey P (2005) Non-ionic surfactant based vesicles (niosomes) for non-invasive topical genetic immunization against hepatitis B. Int J Pharm 296(1–2):80–86
Wacker M, Schubert R (1998) From mixed micelles to liposomes: critical steps during detergent removal by membrane dialysis. Int J Pharm 162(1–2):171–175
Walker W, Brewer JM, Alexander J (1996) Lipid vesicle-entrapped influenza A antigen modulates the influenza A-specific human antibody response in immune reconstituted SCID-human mice. Eur J Immunol 26(7):1664–1667
Yoshida H, Lehr CM, Kok W, Junginger HE, Verhoef JC, Bouwstra JA (1992) Niosomes for oral delivery of peptide drugs. J Control Release 21(1–3):145–153
Yoshioka T, Sternberg B, Florence AT (1994) Preparation and properties of vesicles (niosomes) of sorbitan monoesters (Span 20, 40, 60 and 80) and a sorbitan triester (Span 85). Int J Pharm 105(1):1–6
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2013 Springer Science+Business Media New York
About this chapter
Cite this chapter
Wilkhu, J., Vangala, A., Mohammed, A.R., Perrie, Y. (2013). Designing Nonionic Surfactant Vesicles for the Delivery of Antigens for Systemic and Alternative Delivery Routes. In: Flower, D., Perrie, Y. (eds) Immunomic Discovery of Adjuvants and Candidate Subunit Vaccines. Immunomics Reviews:, vol 5. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-5070-2_11
Download citation
DOI: https://doi.org/10.1007/978-1-4614-5070-2_11
Published:
Publisher Name: Springer, New York, NY
Print ISBN: 978-1-4614-5069-6
Online ISBN: 978-1-4614-5070-2
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)