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Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.
Soema, Peter C; Willems, Geert-Jan; Jiskoot, Wim; Amorij, Jean-Pierre; Kersten, Gideon F.
Afiliación
  • Soema PC; Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands. Electronic address: peter.soema@intravacc.nl.
  • Willems GJ; Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
  • Jiskoot W; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
  • Amorij JP; Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
  • Kersten GF; Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
Eur J Pharm Biopharm ; 94: 427-35, 2015 Aug.
Article en En | MEDLINE | ID: mdl-26144666
ABSTRACT
In this study, the effect of liposomal lipid composition on the physicochemical characteristics and adjuvanticity of liposomes was investigated. Using a design of experiments (DoE) approach, peptide-containing liposomes containing various lipids (EPC, DOPE, DOTAP and DC-Chol) and peptide concentrations were formulated. Liposome size and zeta potential were determined for each formulation. Moreover, the adjuvanticity of the liposomes was assessed in an in vitro dendritic cell (DC) model, by quantifying the expression of DC maturation markers CD40, CD80, CD83 and CD86. The acquired data of these liposome characteristics were successfully fitted with regression models, and response contour plots were generated for each response factor. These models were applied to predict a lipid composition that resulted in a liposome with a target zeta potential. Subsequently, the expression of the DC maturation factors for this lipid composition was predicted and tested in vitro; the acquired maturation responses corresponded well with the predicted ones. These results show that a DoE approach can be used to screen various lipids and lipid compositions, and to predict their impact on liposome size, charge and adjuvanticity. Using such an approach may accelerate the formulation development of liposomal vaccine adjuvants.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proyectos de Investigación / Células Dendríticas / Portadores de Fármacos / Adyuvantes Inmunológicos / Lípidos Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Eur J Pharm Biopharm Asunto de la revista: FARMACIA / FARMACOLOGIA Año: 2015 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Proyectos de Investigación / Células Dendríticas / Portadores de Fármacos / Adyuvantes Inmunológicos / Lípidos Tipo de estudio: Diagnostic_studies / Prognostic_studies / Risk_factors_studies Límite: Humans Idioma: En Revista: Eur J Pharm Biopharm Asunto de la revista: FARMACIA / FARMACOLOGIA Año: 2015 Tipo del documento: Article