Synthesis and Characterization of Self-Assembling Block Copolymers Containing Bioadhesive End Groups

• Published in: Biomacromolecules 2002-03, Vol.3 (2), p.397-406
• Main Authors: Huang, Kui, Lee, Bruce P, Ingram, Dale R, Messersmith, Phillip B
• Format: Article
• Language: English
• Subjects: Calorimetry, Differential Scanning; Dihydroxyphenylalanine - chemistry; Hydrogels - chemistry; Molecular Structure; Poloxamer - chemistry; Polyethylene Glycols - chemistry; Polymers - chemistry; Propylene Glycols - chemistry; Solubility; Temperature
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm015650p

3,4-Dihydroxyphenyl-l-alanine (DOPA) is an unusual amino acid found in mussel adhesive proteins (MAPs) that is believed to lend adhesive characteristics to these proteins. In this paper, we describe a route for the conjugation of DOPA moieties to poly(ethylene oxide)−poly(propylene oxide)−poly(ethylene oxide) (PEO−PPO−PEO) block copolymers. Hydroxyl end groups of PEO−PPO−PEO block copolymers were activated by N,N ‘-disuccinimidyl carbonate and then reacted with DOPA or its methyl ester with high coupling efficiencies from both aqueous and organic solvents. DOPA-modified PEO−PPO−PEO block copolymers were freely soluble in cold water, and dye partitioning and differential scanning calorimetry analysis of these solutions revealed that the copolymers aggregated into micelles at a characteristic temperature that was dependent on block copolymer composition and concentration in solution. Oscillatory rheometry demonstrated that above a block copolymer concentration of approximately 20 wt %, solutions of DOPA-modified PEO−PPO−PEO block copolymers exhibited sol−gel transitions upon heating. The gelation temperature could be tailored between ∼23 and 46 °C by changing the composition, concentration, and molecular weight of the block copolymer. Rheological measurement of the bioadhesive interaction between DOPA-modified Pluronic and bovine submaxillary mucin indicated that DOPA-modified Pluronic was significantly more bioadhesive than unmodified Pluronic.