Uptake Kinetics Of Liposomal Formulations of Differing Charge Influences Development of in Vivo Dendritic Cell Immunotherapy

• Published in: Journal of pharmaceutical sciences 2022-04, Vol.111 (4), p.1081-1091
• Main Authors: Nagy, Noémi Anna, Castenmiller, Charlotte, Vigario, Fernando Lozano, Sparrius, Rinske, van Capel, Toni M.M., de Haas, Aram M., van Kooyk, Yvette, van Ree, Ronald, Tas, Sander W., Geijtenbeek, Teunis B.H., Jiskoot, Wim, Slütter, Bram, de Jong, Esther C.
• Format: Article
• Language: English
• Subjects: Cationic lipid(s); Cell culture; Dendritic Cells; Drug delivery system(s); Immunogenicity; Immunologic Factors; Immunology; Immunotherapy; Immunotherapy - methods; Kinetics; Lipid nanoparticle(s); Liposome(s); Liposomes; Nanomedicine; Skin
• ISSN: 0022-3549; 1520-6017
• DOI: 10.1016/j.xphs.2022.01.022

Dendritic cells (DCs) control adaptive immunity and are therefore attractive for in vivo targeting to either induce immune activation or tolerance, depending on disease. Liposomes, nanoparticles comprised of a lipid bi-layer, provide a nanoplatform for loading disease-relevant antigen, adjuvant and DC-targeting molecules simultaneously. However, it is yet not fully understood how liposomal formulations affect uptake by DCs and DC function. Here, we examined monocyte-derived DC (moDC) and skin DC uptake of six different liposomal formulations, together with their DC-modulating effect. Contrary to literature, we show using imaging flow cytometry that anionic or neutral liposomes are taken up more efficiently than cationic liposomes by moDCs, or by skin DCs after intradermal injection. None of the formulations yielded significant modulation of DC function as determined by the upregulation of maturation markers and cytokine production. These results suggest that anionic liposomes would be more suitable as vaccine carriers for a dermal application.