Biodegradable microcapsules with entrapped DNA for development of new DNA vaccines

Abstract

A general method for the preparation of biodegradable microcapsules capable of antigen inclusion is suggested. Multilayer microcapsules were obtained by the method of level-by-level sorption of various polyelectrolytes (alginate, poly-L-lysine, kappa-carrageenan, and chitosan and dextran derivatives). High inclusion efficiency was found for protein and plasmid DNA (no less than 90%). A series of microcapsules with included pTKShi plasmid that incorporated a genome site encoding the E(2) polypeptide of the classic pig plague virus were obtained for carrying out in vivo experiments. It was shown that introduction to mice of microcapsules with the included pTKShi plasmid induced an immune response. The highest antibody titers of the mouse blood sera were obtained in immunization by microcapsules based on the modified dextran/carrageenan and modified chitosan/carrageenan. The method of antigen inclusion into biodegradable microcapsules could be used for the development of encapsulated vaccines of a new generation (DNA vaccines).

Polymeric Multilayer Capsules in Drug Delivery

“…Although no analysis of T-cell responses was performed in this study, antibody titers appeared elevated compared to immunization with naked plasmid DNA, thus indicating that PMLCs might also be beneficial for enhancing the efficiency of immunization protocols involving DNA. [203] Finally, an additional benefit of using PMLCs as antigen-delivery vehicles is the high versatility of the LbL technique itself, which allows one to modify the surface of the microcapsules with nearly any ligand of interest. Such an approach might be useful for enhancing specific cellular targeting by linking the microcapsules to antibodies, or to enhance the activation of dendritic cells by coating the microcapsules with immunopotentiators such as synthetic Toll-like receptor agonists.…”

“Wrapped Up” Vaccines in the Context of HIV-1 Immunotherapy

“…Polyethyleneimine (PEI) has been extensively used to deliver pDNA and siRNA to cells [221][222][223]. PEI consists of repeating units that contain two carbon atoms and a protonatable nitrogen atom.…”

Wirkstoffverabreichung mithilfe polymerer Mehrschichtkapseln

“…Dies deutet auf Vorteile von Mehrschichtkapseln auch bei der Immunisierung mit DNA hin. [203] Ein weiterer Vorteil der Kapseln als Antigenvehikel ist schließlich die enorme Vielseitigkeit des LbL-Verfahrens: [145] Polymere Mehrschichtkapseln Angewandte Chemie Die Oberfläche der Kapseln kann in nahezu beliebiger Weise funktionalisiert werden. So könnten die Kapseln mit Antikörpern verknüpft werden, die spezifische Ziele ansteuern, oder sie könnten dendritische Zellen besser aktivieren, indem sie mit Immunverstärkern wie synthetischen Agonisten der Signaltransduktions-vermittelnden Mustererkennungsrezeptoren (Toll-artigen Rezeptoren) beschichtet werden.…”