{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,23]],"date-time":"2025-10-23T16:35:12Z","timestamp":1761237312250,"version":"3.28.0"},"reference-count":38,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2006,6,1]],"date-time":"2006-06-01T00:00:00Z","timestamp":1149120000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2006,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Vesicular adjuvant systems composing dimethyldioctadecylammonium (DDA) can promote both cell-mediated and humoral immune responses to the tuberculosis vaccine fusion protein in mice. However, these DDA preparations were found to be physically unstable, forming aggregates under ambient storage conditions. Therefore there is a need to improve the stability of such systems without undermining their potent adjuvanticity. To this end, the effect of incorporating non-ionic surfactants, such as 1-monopalmitoyl glycerol (MP), in addition to cholesterol (Chol) and trehalose 6,60-dibehenate (TDB), on the stability and efficacy of these vaccine delivery systems was investigated. Differential scanning calorimetry revealed a reduction in the phase transition temperature (Tc) of DDA-based vesicles by \u223c12\u00b0C when MP and cholesterol (1:1 molar ratio) were incorporated into the DDA system. Transmission electron microscopy (TEM) revealed the addition of MP to DDA vesicles resulted in the formation of multi-lamellar vesicles. Environmental scanning electron microscopy (ESEM) of MP-Chol-DDA-TDB (16:16:4:0.5 \u03bcmol) indicated that incorporation of antigen led to increased stability of the vesicles, perhaps as a result of the antigen embedding within the vesicle bilayers. At 4\u00b0C DDA liposomes showed significant vesicle aggregation after 28 days, although addition of MP-Chol or TDB was shown to inhibit this instability. Alternatively, at 25\u00b0C only the MP-based systems retained their original size. The presence of MP within the vesicle formulation was also shown to promote a sustained release of antigen in-vitro. The adjuvant activity of various systems was tested in mice against three subunit antigens, including mycobacterial fusion protein Ag85B-ESAT-6, and two malarial antigens (Merozoite surface protein 1, MSP1, and the glutamate rich protein, GLURP). The MP-and DDA-based systems induced antibody responses at comparable levels whereas the DDA-based systems induced more powerful cell-mediated immune responses.<\/jats:p>","DOI":"10.1211\/jpp.58.6.0009","type":"journal-article","created":{"date-parts":[[2006,5,20]],"date-time":"2006-05-20T17:22:36Z","timestamp":1148145756000},"page":"787-799","source":"Crossref","is-referenced-by-count":71,"title":["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"],"prefix":"10.1093","volume":"58","author":[{"given":"Anil","family":"Vangala","sequence":"first","affiliation":[{"name":"Medicines Research Unit, School of Life and Health Sciences, Aston University , Birmingham, B4 7ET,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel","family":"Kirby","sequence":"additional","affiliation":[{"name":"Medicines Research Unit, School of Life and Health Sciences, Aston University , Birmingham, B4 7ET,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ida","family":"Rosenkrands","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , DK-2300 Copenhagen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Else Marie","family":"Agger","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , DK-2300 Copenhagen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Andersen","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease Immunology, Adjuvant Research, Statens Serum Institut , DK-2300 Copenhagen,","place":["Denmark"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yvonne","family":"Perrie","sequence":"additional","affiliation":[{"name":"Medicines Research Unit, School of Life and Health Sciences, Aston University , Birmingham, B4 7ET,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2006,6,1]]},"reference":[{"key":"2024103109351014900_cit1","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1128\/iai.59.4.1558-1563.1991","article-title":"T-cell proliferative response to antigens secreted by Mycobacterium tuberculosis","volume":"59","author":"Andersen","year":"1991","journal-title":"Infect. Immun."},{"key":"2024103109351014900_cit2","doi-asserted-by":"crossref","first-page":"1241","DOI":"10.1016\/0264-410X(94)90251-8","article-title":"Activation of systemic and mucosal immune response following nasal administration of liposomes","volume":"12","author":"Aramaki","year":"1994","journal-title":"Vaccine"},{"key":"2024103109351014900_cit3","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0378-5173(00)00362-8","article-title":"The effect of processing variables on the physical characteristics of non-ionic surfactant vesicles (niosomes) formed from a hexadecyl diglycerol ether","volume":"201","author":"Arunothayanun","year":"2000","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit4","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1016\/S0022-2836(65)80093-6","article-title":"Diffusion of univalent ions across the lamellae of swollen phospholipids","volume":"13","author":"Bangham","year":"1965","journal-title":"J. Mol. Biol."},{"key":"2024103109351014900_cit5","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1017\/S0033583500003735","article-title":"Physical-properties of the fluid lipid-bilayer component of cell membranes \u2014 a perspective","volume":"24","author":"Bloom","year":"1991","journal-title":"Q. Rev. Biophys."},{"key":"2024103109351014900_cit6","first-page":"570","article-title":"The adjuvant activity of non-ionic surfactant vesicles (niosomes) on the BALB\/c humoral response to bovine serum albumin","volume":"75","author":"Brewer","year":"1992","journal-title":"Immunology"},{"key":"2024103109351014900_cit7","doi-asserted-by":"crossref","first-page":"733","DOI":"10.1038\/192733a0","article-title":"\u03b3 globulin and acquired immunity to human malaria","volume":"192","author":"Cohen","year":"1961","journal-title":"Nature"},{"key":"2024103109351014900_cit8","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1016\/S0378-5173(97)00289-5","article-title":"The evaluation of crown ether based niosomes as cation containing and cation sensitive drug delivery systems","volume":"159","author":"Darwish","year":"1997","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit9","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.bbamem.2005.10.011","article-title":"Characterization of cationic liposomes based on dimethyldioctadecylammonium and synthetic cord factor from M. tuberculosis (trehalose 6,6\u2032-dibehenate) \u2014 a novel adjuvant inducing both strong CMI and antibody responses","volume":"1718","author":"Davidsen","year":"2005","journal-title":"Biochim. Biophys. Acta."},{"key":"2024103109351014900_cit10","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0009-3084(02)00176-7","article-title":"The arrangement of cholesterol in membranes and binding of NAP-22","volume":"122","author":"Egelhaaf","year":"2003","journal-title":"Chem. Phys. Lipids"},{"key":"2024103109351014900_cit11","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0009-3084(00)00127-4","article-title":"Phase transition in dioctadecyldimethylammonium bromide and chloride vesicles prepared by different methods","volume":"105","author":"Feitosa","year":"2000","journal-title":"Chem. Phys. Lipids"},{"key":"2024103109351014900_cit12","doi-asserted-by":"crossref","first-page":"65","DOI":"10.3109\/10611869509015936","article-title":"Factors affecting the oral uptake and translocation of polystyrene nanoparticles: histological and analytical evidence","volume":"3","author":"Florence","year":"1995","journal-title":"J. Drug Target."},{"key":"2024103109351014900_cit13","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1006\/jcis.1995.1406","article-title":"Morphological features in 1-monoglyceride monolayers","volume":"174","author":"Gehlert","year":"1995","journal-title":"J. Coll. Interf. Sci."},{"key":"2024103109351014900_cit14","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/S0378-5173(96)04840-5","article-title":"Pharmaceutical and biological characterisation of a doxorubicin-polymer conjugate (PK1) entrapped in sorbitan monostearate Span 60 niosomes","volume":"148","author":"Gianasi","year":"1997","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit15","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/0167-5699(90)90034-7","article-title":"Immunological adjuvants: a role for liposomes","volume":"11","author":"Gregoriadis","year":"1990","journal-title":"Immunol. Today"},{"key":"2024103109351014900_cit16","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/0264-410X(93)90190-9","article-title":"Adjuvants \u2014 a balance between toxicity and adjuvanticity","volume":"11","author":"Gupta","year":"1993","journal-title":"Vaccine"},{"key":"2024103109351014900_cit17","doi-asserted-by":"crossref","first-page":"73","DOI":"10.1016\/S0378-5173(02)00301-0","article-title":"Studies on a high encapsulation of colchicine by a niosome system","volume":"244","author":"Hao","year":"2002","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit18","doi-asserted-by":"crossref","first-page":"1608","DOI":"10.1128\/IAI.72.3.1608-1617.2004","article-title":"Combination of the cationic surfactant dimethyl dioctadecyl ammonium bromide and synthetic myco-bacterial cord factor as an efficient adjuvant for tuberculosis subunit vaccines","volume":"72","author":"Holten-Andersen","year":"2004","journal-title":"Infect. Immun."},{"key":"2024103109351014900_cit19","doi-asserted-by":"crossref","first-page":"1107","DOI":"10.5650\/jos1996.49.1107","article-title":"Supramolecular structure of functionality vesicles: niosome formation of nonionic amphiphiles and physico-chemical properties in aqueous dispersion","volume":"49","author":"Horiuchi","year":"2000","journal-title":"J. Jpn. Oil Chem. Soc."},{"article-title":"Intermolecular and surface forces","year":"1993","author":"Israelachvili","key":"2024103109351014900_cit20"},{"key":"2024103109351014900_cit21","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/0005-2736(77)90099-2","article-title":"Theory of self assembly of lipid bilayers and vesicles","volume":"470","author":"Israelachvili","year":"1977","journal-title":"Biochim. Biophys. Acta."},{"key":"2024103109351014900_cit22","first-page":"979","article-title":"Dehydration-rehydration vesicles: a simple method for high yield drug entrapment in liposomes","volume":"2","author":"Kirby","year":"1984","journal-title":"Biotechnology"},{"key":"2024103109351014900_cit23","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1128\/iai.65.2.623-629.1997","article-title":"Adjuvant modulation of immune responses to tuberculosis sub-unit vaccines","volume":"65","author":"Lindblad","year":"1997","journal-title":"Infect. Immun."},{"key":"2024103109351014900_cit24","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/S0968-4328(99)00146-8","article-title":"Liposomes as protective agents of stratum corneum against octyl glucosides: a study based on high resolution, low temperature scanning electron microscopy","volume":"32","author":"Lopez","year":"2001","journal-title":"Micron"},{"key":"2024103109351014900_cit25","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.ijpharm.2004.07.010","article-title":"Liposome formulation of poorly water soluble drugs: optimisation of drug loading and ESEM analysis of stability","volume":"285","author":"Mohammed","year":"2004","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit26","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/0264-410X(93)90011-L","article-title":"Biodegradable microparticles for oral immunization","volume":"11","author":"O'Hagan","year":"1993","journal-title":"Vaccine"},{"key":"2024103109351014900_cit27","doi-asserted-by":"crossref","first-page":"2773","DOI":"10.1128\/IAI.69.5.2773-2778.2001","article-title":"Protection of mice with a tuberculosis subunit vaccine based on a fusion protein of antigen 85B and ESAT-6","volume":"69","author":"Olsen","year":"2001","journal-title":"Infect. Immun."},{"key":"2024103109351014900_cit28","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1111\/j.2042-7158.1988.tb05263.x","article-title":"The distribution of doxorubicin in mice following administration in niosomes","volume":"40","author":"Rogerson","year":"1988","journal-title":"J. Pharm. Pharmacol."},{"key":"2024103109351014900_cit29","doi-asserted-by":"crossref","first-page":"5817","DOI":"10.1128\/IAI.73.9.5817-5826.2005","article-title":"Cationic liposomes containing mycobacterial lipids: a new powerful Th1 adjuvant system","volume":"73","author":"Rosenkrands","year":"2005","journal-title":"Infect. Immun."},{"key":"2024103109351014900_cit30","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1128\/cdli.2.1.30-34.1995","article-title":"Antigenicity and immunogenicity of recombinant glutamate-rich protein of Plasmodium falciparum expressed in Escherichia coli","volume":"2","author":"Theisen","year":"1995","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"2024103109351014900_cit31","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0378-5173(97)00141-5","article-title":"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","volume":"155","author":"Uchegbu","year":"1997","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0001-8686(95)00242-I","article-title":"Non-ionic surfactant vesicles (niosomes): physical and pharmaceutical chemistry","volume":"58","author":"Uchegbu","year":"1995","journal-title":"Adv. Coll. Interf. Sci."},{"key":"2024103109351014900_cit33","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/S0378-5173(98)00169-0","article-title":"Non-ionic surfactant based vesicles (niosomes) in drug delivery","volume":"172","author":"Uchegbu","year":"1998","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit34","first-page":"33","article-title":"Phase-transitions in aqueous dispersions of the hexadecyl diglycerol ether (C(16)g(2)) non-ionic surfactant, cholesterol and cholesteryl poly-24-oxyethylene ether-vesicles, tubules, discomes and micelles","volume":"6","author":"Uchegbu","year":"1996","journal-title":"STP Pharm. Sci."},{"key":"2024103109351014900_cit35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/0378-5173(94)90228-3","article-title":"Preparation and properties of vesicles (niosomes) of sorbitan monoesters (Span 20, 40, 60, and 80) and a sorbitan triester (Span 85)","volume":"105","author":"Yoshioka","year":"1994","journal-title":"Int. J. Pharm."},{"key":"2024103109351014900_cit36","doi-asserted-by":"crossref","first-page":"491","DOI":"10.3109\/08982109709035518","article-title":"Scanning tunnelling microscopy investigation of liposome-DNA-Ca2+ complexes","volume":"7","author":"Zareie","year":"1997","journal-title":"J. Liposome Res."},{"key":"2024103109351014900_cit37","doi-asserted-by":"crossref","first-page":"220","DOI":"10.4049\/jimmunol.138.1.220","article-title":"Adjuvant effects of nonionic block polymer surfactant on liposome-induced humoral immune response","volume":"138","author":"Zigterman","year":"1987","journal-title":"J. Immun."},{"key":"2024103109351014900_cit38","first-page":"37","article-title":"Stimulation of liposome induced humoral responses by non ionic block polymer surfactants in Xid mice","volume":"65","author":"Zigterman","year":"1988","journal-title":"Immunology"}],"container-title":["Journal of Pharmacy and Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1211%2Fjpp.58.6.0009","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/58\/6\/787\/60255275\/jpp.58.6.0009.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jpp\/article-pdf\/58\/6\/787\/60255275\/jpp.58.6.0009.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,31]],"date-time":"2024-10-31T09:39:40Z","timestamp":1730367580000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jpp\/article\/58\/6\/787\/6147768"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2006,6,1]]},"references-count":38,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2006,6,1]]},"published-print":{"date-parts":[[2006,6,1]]}},"URL":"https:\/\/doi.org\/10.1211\/jpp.58.6.0009","relation":{},"ISSN":["0022-3573","2042-7158"],"issn-type":[{"type":"print","value":"0022-3573"},{"type":"electronic","value":"2042-7158"}],"subject":[],"published-other":{"date-parts":[[2006,6]]},"published":{"date-parts":[[2006,6,1]]}}}