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

Defense Date

8-2-2006

Graduation Date

Spring 1-1-2006

Availability

Campus Only

Submission Type

thesis

Degree Name

MS

Department

Pharmaceutics

School

School of Pharmacy

Committee Chair

Wilson S. Meng

Committee Member

Christopher K. Surratt

Committee Member

James K. Drennen

Keywords

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

Abstract

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.

Format

PDF

Language

English

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