title: Predicting the influence of liposomal lipid composition on liposome size, zeta potential and liposome-induced dendritic cell maturation using a design of experiments approach.
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.
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands. Electronic address: peter.soema@intravacc.nl.
authors.forename: Peter C
authors.initials: PC
authors.lastname: Soema
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
authors.forename: Geert-Jan
authors.initials: GJ
authors.lastname: Willems
authors.affiliation: Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Wim
authors.initials: W
authors.lastname: Jiskoot
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Amorij
authors.affiliation: Intravacc (Institute for Translational Vaccinology), Bilthoven, The Netherlands; Division of Drug Delivery Technology, Leiden Academic Centre for Drug Research, Leiden University, Leiden, The Netherlands.
authors.forename: Gideon F
authors.initials: GF
authors.lastname: Kersten
mesh_terms: D000276:Adjuvants, Immunologic / Q000737:chemistry* / Q000494:pharmacology; D015703:Antigens, CD / Q000096:biosynthesis; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000187:drug effects* / Q000276:immunology; D004337:Drug Carriers / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry* / Q000494:pharmacology; D008081:Liposomes; D018448:Models, Immunological; D010316:Particle Size; D011379:Prognosis; D012044:Regression Analysis; D012107:Research Design; D013499:Surface Properties; D014612:Vaccines / Q000008:administration & dosage
chemical_list: D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D004337:Drug Carriers; D008055:Lipids; D008081:Liposomes; D014612:Vaccines
keywords: Cationic lipids; Dendritic cells; Design of experiments; Liposomes; Maturation markers; Prediction models