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PEGylated dextran as long-circulating pharmaceutical carrier
Anatoly N Lukyanov1, Rishikesh M Sawant, William C Hartner
1Department of Pharmaceutical Sciences, Bouve College of Health Sciences, 312 Mugar Building, Northeastern University, Boston, MA 02115, USA.
Journal of Biomaterials Science. Polymer Edition
|July 22, 2004
Summary
Synthesizing dextran-polyethylene glycol (PEG) conjugates enhances circulation time and reduces liver uptake. These PEGylated dextran polymers offer a promising platform for developing long-circulating pharmaceutical preparations.
Area of Science:
- Biomaterials Science
- Polymer Chemistry
- Drug Delivery Systems
Background:
- Dextran is a polysaccharide with potential pharmaceutical applications.
- Non-modified dextran is rapidly cleared from circulation, limiting its therapeutic use.
- Polyethylene glycol (PEG)ylation is a common strategy to improve polymer pharmacokinetics.
Purpose of the Study:
- To synthesize dextran-polyethylene glycol (PEG) conjugates.
- To evaluate the impact of PEGylation on dextran's circulation half-life and organ uptake.
- To explore the potential of dextran-PEG conjugates as a platform for long-circulating pharmaceuticals.
Main Methods:
- Dextran hydroxy groups were activated using carbonyldiimidazole.
- Ethylenediamine was used to introduce amino groups onto dextran.
- Amino groups were reacted with a succinimidyl-activated PEG derivative to form conjugates.
- PEGylated dextran conjugates were characterized for PEG residue number and molecular weight.
Main Results:
- Dextran-PEG conjugates with average of 12 and 21 PEG (5 kDa) residues per dextran (73 kDa) molecule were successfully synthesized.
- Circulation half-lives were significantly increased: 5.3 h and 7.0 h for PEGylated dextran, compared to 4.0 h for non-PEGylated dextran.
- PEGylation of dextran inhibited its uptake by the liver, a key organ of the reticuloendothelial system.
Conclusions:
- Dextran-PEG conjugates demonstrate prolonged circulation times in vivo.
- PEGylation effectively reduces the clearance of dextran by the reticuloendothelial system.
- Dextran-PEG conjugates represent a viable and convenient platform for developing sustained-release pharmaceutical formulations.