title: Stable cationic microparticles for enhanced model antigen delivery to dendritic cells.
abstract: The objectives of this work were (i) to prepare physically stable cationic microparticles and (ii) to study the impact of the surface properties on microparticle phagocytosis and the phenotype of dendritic cells (DC). Protein loaded biodegradable microparticles from poly(lactic-co-glycolic acid) [PLGA] were produced in a micromixer-based w/o/w solvent evaporation procedure. Anionic particles were obtained by using polyvinyl alcohol (PVA) as stabilizing agent; for cationic surfaces cetyltrimethylammonium bromide (CTAB) and chitosan/PVA or DEAE-dextran/PVA blends were evaluated. In phagocytosis studies human monocytes and monocyte-derived DC were incubated with microparticles and analysed by flow cytometry. While CTAB modified microparticles lost their positive charge and aggregated due to CTAB desorption from the particle surface, the modification with chitosan and DEAE-dextran resulted in stable microparticles without cell toxicity. Due to a very low endotoxin content, phagocytosis of anionic and cationic microparticles did not induce an upregulation of maturation-associated surface markers on DC. DEAE-dextran modified microparticles showed an enhanced model protein delivery into phagocytic cells. Overall, PLGA microparticles are suitable vehicles for protein delivery to DC, which might be used for DC-based cell therapies.
authors.affiliation: Department of Pharmacy, Free University of Berlin, Kelchstrasse 31, D-12169 Berlin, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Wischke
authors.forename: Hans-Hubert
authors.initials: HH
authors.lastname: Borchert
authors.forename: Julian
authors.initials: J
authors.lastname: Zimmermann
authors.forename: Ingo
authors.initials: I
authors.lastname: Siebenbrodt
authors.forename: Dirk R
authors.initials: DR
authors.lastname: Lorenzen
mesh_terms: D000941:Antigens / Q000008:administration & dosage* / Q000378:metabolism; D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D000077286:Cetrimonium; D002593:Cetrimonium Compounds / Q000737:chemistry / Q000633:toxicity; D048271:Chitosan / Q000008:administration & dosage; D003637:DEAE-Dextran / Q000008:administration & dosage; D003713:Dendritic Cells / Q000276:immunology / Q000378:metabolism*; D016503:Drug Delivery Systems; D005079:Excipients; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D019344:Lactic Acid / Q000008:administration & dosage*; D008562:Membrane Glycoproteins / Q000032:analysis; D010316:Particle Size; D010587:Phagocytosis; D011100:Polyglycolic Acid / Q000008:administration & dosage*; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000008:administration & dosage*; D013499:Surface Properties; D000097802:CD83 Antigen
chemical_list: D000941:Antigens; D015703:Antigens, CD; D000077286:Cetrimonium; D002593:Cetrimonium Compounds; D048271:Chitosan; D003637:DEAE-Dextran; D005079:Excipients; D007136:Immunoglobulins; D019344:Lactic Acid; D008562:Membrane Glycoproteins; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers; D000097802:CD83 Antigen