title: Encapsulation of antigen-loaded silica nanoparticles into microparticles for intradermal powder injection.
abstract: Epidermal powder immunisation (EPI) is being investigated as a promising needle-free delivery methods for vaccination. The objective of this work was to prepare a nanoparticles-in-microparticles (nano-in-micro) system, integrating the advantages of nanoparticles and microparticles into one vaccine delivery system for epidermal powder immunisation. Cationic mesoporous silica nanoparticles (MSNP-NH2) were prepared and loaded with ovalbumin as a model antigen. Loading was driven by electrostatic interactions. Ovalbumin-loaded silica nanoparticles were subsequently formulated into sugar-based microparticles by spray-freeze-drying. The obtained microparticles meet the size requirement for EPI. Confocal microscopy was used to demonstrate that the nanoparticles are homogeneously distributed in the microparticles. Furthermore, the silica nanoparticles in the dry microparticles can be re-dispersed in aqueous solution showing no aggregation. The recovered ovalbumin shows integrity compared to native ovalbumin. The present nano-in-micro system allows (1) nanoparticles to be immobilized and finely distributed in microparticles, (2) microparticle formation and (3) re-dispersion of nanoparticles without subsequent aggregation. The nanoparticles inside microparticles can (1) adsorb proteins to cationic shell/surface voids in spray-dried products without detriment to ovalbumin stability, (2) deliver antigens in nano-sized modes to allow recognition by the immune system.
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilians-University Munich, Butenandtstrasse 5, D-81377 Munich, Germany.
authors.forename: Yibin
authors.initials: Y
authors.lastname: Deng
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilians-University Munich, Butenandtstrasse 5, D-81377 Munich, Germany.
authors.forename: Roman
authors.initials: R
authors.lastname: Mathaes
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilians-University Munich, Butenandtstrasse 5, D-81377 Munich, Germany.
authors.forename: Gerhard
authors.initials: G
authors.lastname: Winter
authors.affiliation: Department of Pharmacy, Pharmaceutical Technology & Biopharmaceutics, Ludwig-Maximilians-University Munich, Butenandtstrasse 5, D-81377 Munich, Germany. Electronic address: julia.engert@cup.uni-muenchen.de.
authors.forename: Julia
authors.initials: J
authors.lastname: Engert
mesh_terms: D000818:Animals; D000941:Antigens / Q000737:chemistry*; D002460:Cell Line; D004337:Drug Carriers; D016503:Drug Delivery Systems / Q000379:methods*; D007271:Injections, Intradermal; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D010047:Ovalbumin / Q000737:chemistry*; D010316:Particle Size; D016062:Porosity; D011208:Powders / Q000008:administration & dosage*; D012822:Silicon Dioxide / Q000737:chemistry*; D013499:Surface Properties
chemical_list: D000941:Antigens; D004337:Drug Carriers; D011208:Powders; D012822:Silicon Dioxide; D010047:Ovalbumin
keywords: Mesoporous silica; Microparticles; Nano-in-microparticle system; Nanoparticles; Vaccination