Development of particle-based systems for the delivery of oligonucleotides into primary dendritic cells

<p>The purpose of this research was to develop a particulate-based vector for delivery of oligonucleotides (ODN) into dendritic cells using a cationic peptide (O10H6) to provide enhanced delivery. Anchoring of O10H6-ODN condensates was hypothesized to provide increased intracellular ODN accumulation required in decoy therapy. The self-assembling delivery system consisting of carboxylate-modified polystyrene microspheres (MS) coated with a short cationic peptide (O10H6) was shown to effectively deliver ODN to DCs. The MS serves to stabilize O10H6 and ODN complexation and remains a colloidal dispersion upon addition of condensates. Nanoparticles of poly (d, l-lactide-co-glycolide) are biodegradable particulates that provide the ability to entrap O10H6-ODN condensates and protect DNA. These particles loaded with DNA condensates were also shown to enhance delivery of ODN to DCs. The ability of ODN to escape the endosomal pathway upon accumulation in DCs is observed for both MSO10H6-ODN and PLGAO10H6-ODN. Taken together, these data support MSo10H6-ODN and PLGAO10H6-ODN as novel particulate-based vectors for oligonucleotide delivery to dendritic cells.</p>

Name thesis:degree_name

MS

Level thesis:degree_level

Campus Only

Discipline thesis:degree_discipline

Pharmaceutics

Year dc:date.available

2006

Author dc:creator

• Kovacs, Jeffrey Ryan

Contributors dc:contributor

• Wilson S. Meng
• Christopher K. Surratt
• James K. Drennen

• Dendritic cells
• Oligonucleotides
• Polystyrene Migrospheres
• Poly(lactic-co-glycolic acid) nano particles

Language dc:language

English

Repository record dc:identifier

https://dsc.duq.edu/etd/1593

OAI identifier oai:identifier

oai:dsc.duq.edu:etd-2610