Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach

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Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles : A quality-by-design approach. / Rose, Fabrice; Wern, Jeanette Erbo; Ingvarsson, Pall Thor; van de Weert, Marco; Andersen, Peter; Follmann, Frank; Foged, Camilla.

In: Journal of controlled release : official journal of the Controlled Release Society, Vol. 210, 2015, p. 48-57.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Rose, F, Wern, JE, Ingvarsson, PT, van de Weert, M, Andersen, P, Follmann, F & Foged, C 2015, 'Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach', Journal of controlled release : official journal of the Controlled Release Society, vol. 210, pp. 48-57. https://doi.org/10.1016/j.jconrel.2015.05.004

APA

Rose, F., Wern, J. E., Ingvarsson, P. T., van de Weert, M., Andersen, P., Follmann, F., & Foged, C. (2015). Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach. Journal of controlled release : official journal of the Controlled Release Society, 210, 48-57. https://doi.org/10.1016/j.jconrel.2015.05.004

Vancouver

Rose F, Wern JE, Ingvarsson PT, van de Weert M, Andersen P, Follmann F et al. Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach. Journal of controlled release : official journal of the Controlled Release Society. 2015;210:48-57. https://doi.org/10.1016/j.jconrel.2015.05.004

Author

Rose, Fabrice ; Wern, Jeanette Erbo ; Ingvarsson, Pall Thor ; van de Weert, Marco ; Andersen, Peter ; Follmann, Frank ; Foged, Camilla. / Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles : A quality-by-design approach. In: Journal of controlled release : official journal of the Controlled Release Society. 2015 ; Vol. 210. pp. 48-57.

Bibtex

@article{51c6176706eb4c32975a69527cb1266c,
title = "Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles: A quality-by-design approach",
abstract = "The purpose of this study was to design a novel and versatile adjuvant intended for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity characterized by antibodies and Th1/Th17 responses. Such responses are important for the protection against diseases caused by intracellular bacteria such as Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were engineered using an oil-in-water single emulsion method and a quality-by-design approach was adopted to define the optimal operating space (OOS). Four critical process parameters (CPPs) were identified, including the acetone concentration in the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid-to-total solid ratio, and the total concentration. The CPPs were linked to critical quality attributes consisting of the particle size, polydispersity index (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A central composite face-centered design was performed followed by multiple linear regression analysis. The size, PDI, enthalpy of the phase transition and yield were successfully modeled, whereas the models for the zeta-potential and the stability were poor. Cryo-transmission electron microscopy revealed that the main structural effect on the nanoparticle architecture is caused by the use of PVA, and two different morphologies were identified: i) A PLGA core coated with one or several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid membrane structures. The optimal formulation, identified from the OOS, was evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses that were similar in quality and magnitude to the response induced by DDA/TDB liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the PLGA hybrid matrix. This study demonstrates the complexity of formulation design for the engineering of a hybrid lipid-polymer nanoparticle adjuvant.",
author = "Fabrice Rose and Wern, {Jeanette Erbo} and Ingvarsson, {Pall Thor} and {van de Weert}, Marco and Peter Andersen and Frank Follmann and Camilla Foged",
note = "Copyright {\textcopyright} 2015 Elsevier B.V. All rights reserved.",
year = "2015",
doi = "10.1016/j.jconrel.2015.05.004",
language = "English",
volume = "210",
pages = "48--57",
journal = "Journal of Controlled Release",
issn = "0168-3659",
publisher = "Elsevier",

}

RIS

TY - JOUR

T1 - Engineering of a novel adjuvant based on lipid-polymer hybrid nanoparticles

T2 - A quality-by-design approach

AU - Rose, Fabrice

AU - Wern, Jeanette Erbo

AU - Ingvarsson, Pall Thor

AU - van de Weert, Marco

AU - Andersen, Peter

AU - Follmann, Frank

AU - Foged, Camilla

N1 - Copyright © 2015 Elsevier B.V. All rights reserved.

PY - 2015

Y1 - 2015

N2 - The purpose of this study was to design a novel and versatile adjuvant intended for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity characterized by antibodies and Th1/Th17 responses. Such responses are important for the protection against diseases caused by intracellular bacteria such as Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were engineered using an oil-in-water single emulsion method and a quality-by-design approach was adopted to define the optimal operating space (OOS). Four critical process parameters (CPPs) were identified, including the acetone concentration in the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid-to-total solid ratio, and the total concentration. The CPPs were linked to critical quality attributes consisting of the particle size, polydispersity index (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A central composite face-centered design was performed followed by multiple linear regression analysis. The size, PDI, enthalpy of the phase transition and yield were successfully modeled, whereas the models for the zeta-potential and the stability were poor. Cryo-transmission electron microscopy revealed that the main structural effect on the nanoparticle architecture is caused by the use of PVA, and two different morphologies were identified: i) A PLGA core coated with one or several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid membrane structures. The optimal formulation, identified from the OOS, was evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses that were similar in quality and magnitude to the response induced by DDA/TDB liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the PLGA hybrid matrix. This study demonstrates the complexity of formulation design for the engineering of a hybrid lipid-polymer nanoparticle adjuvant.

AB - The purpose of this study was to design a novel and versatile adjuvant intended for mucosal vaccination based on biodegradable poly(DL-lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) modified with the cationic surfactant dimethyldioctadecylammonium (DDA) bromide and the immunopotentiator trehalose-6,6'-dibehenate (TDB) (CAF01) to tailor humoral and cellular immunity characterized by antibodies and Th1/Th17 responses. Such responses are important for the protection against diseases caused by intracellular bacteria such as Chlamydia trachomatis and Mycobacterium tuberculosis. The hybrid NPs were engineered using an oil-in-water single emulsion method and a quality-by-design approach was adopted to define the optimal operating space (OOS). Four critical process parameters (CPPs) were identified, including the acetone concentration in the water phase, the stabilizer [polyvinylalcohol (PVA)] concentration, the lipid-to-total solid ratio, and the total concentration. The CPPs were linked to critical quality attributes consisting of the particle size, polydispersity index (PDI), zeta-potential, thermotropic phase behavior, yield and stability. A central composite face-centered design was performed followed by multiple linear regression analysis. The size, PDI, enthalpy of the phase transition and yield were successfully modeled, whereas the models for the zeta-potential and the stability were poor. Cryo-transmission electron microscopy revealed that the main structural effect on the nanoparticle architecture is caused by the use of PVA, and two different morphologies were identified: i) A PLGA core coated with one or several concentric lipid bilayers, and ii) a PLGA nanoshell encapsulating lipid membrane structures. The optimal formulation, identified from the OOS, was evaluated in vivo. The hybrid NPs induced antibody and Th1/Th17 immune responses that were similar in quality and magnitude to the response induced by DDA/TDB liposomes, showing that the adjuvant properties of DDA/TDB are maintained in the PLGA hybrid matrix. This study demonstrates the complexity of formulation design for the engineering of a hybrid lipid-polymer nanoparticle adjuvant.

U2 - 10.1016/j.jconrel.2015.05.004

DO - 10.1016/j.jconrel.2015.05.004

M3 - Journal article

C2 - 25957906

VL - 210

SP - 48

EP - 57

JO - Journal of Controlled Release

JF - Journal of Controlled Release

SN - 0168-3659

ER -

ID: 139033805