Characterization of particles fabricated with poly(D, L-lactic-co-glycolic acid) and an ornithine-histidine peptide as carriers of oligodeoxynucleotide for delivery into primary dendritic cells.
We report the formulation of particles to deliver oligodeoxynucleotides (ODN) into primary murine dendritic cells (DCs), the most potent antigen-presenting cells (APCs) known, using poly(D,L-lactic-co-glycolic acid) (PLGA) and a small cationic peptide. PLGA polymer and the ODN were fabricated into nano-sized spherical particles with the aid of O10H6 (O = ornithine, H = histidine). We have previously determined that O10H6 condenses DNA and is less toxic to DCs than a similar lysine-based peptide. The colloidal particles are stabilized by negative surface potentials. The peptide and the ODN can be detected in the fabricated particles with reflectance infrared spectroscopy. Significant ODN uptake can be observed in DCs exposed to the particles. Confocal imaging studies reveal that ODN can be internalized and escape from lysosomes in DCs. Taken together, these data suggest that combining PLGA and O10H6 is a feasible method to generate ODN-containing nano-sized particles for applications in DCs.
Zheng
Ying
Y
Division of Pharmaceutical Sciences, Duquesne University, Mellon Hall 413, 600 Forbes Avenue, Pittsburgh, PA 15282, USA.
Kovacs
Jeffrey R
JR
Gawalt
Ellen S
ES
Shen
Hongmei
H
Meng
Wilson S
WS
D000818:Animals; D002478:Cells, Cultured; D003713:Dendritic Cells / Q000378:metabolism*; D004337:Drug Carriers / Q000737:chemistry* / Q000627:therapeutic use; D006016:Glycolates / Q000627:therapeutic use*; D006639:Histidine; D019344:Lactic Acid; D008247:Lysosomes; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000008:administration & dosage* / Q000493:pharmacokinetics; D009952:Ornithine; D010455:Peptides / Q000627:therapeutic use*; D011100:Polyglycolic Acid; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer
D004337:Drug Carriers; D006016:Glycolates; D009838:Oligodeoxyribonucleotides; D010455:Peptides; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D006639:Histidine; D009952:Ornithine