Synthesis and characterization of self-assembling block copolymers containing bioadhesive end groups.
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 approximately 23 and 46 degrees 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.
Huang
Kui
K
Biomedical Engineering Department, Robert R. McCormick School of Engineering and Applied Sciences, Northwestern University, 2145 Sheridan Road, Evanston, Illinois 60208, USA.
Lee
Bruce P
BP
Ingram
Dale R
DR
Messersmith
Phillip B
PB
D002152:Calorimetry, Differential Scanning; D004295:Dihydroxyphenylalanine / Q000737:chemistry; D020100:Hydrogels / Q000737:chemistry; D015394:Molecular Structure; D020442:Poloxamer / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000737:chemistry*; D011108:Polymers / Q000737:chemistry*; D011409:Propylene Glycols / Q000737:chemistry*; D012995:Solubility; D013696:Temperature
D020100:Hydrogels; C116176:PEO-PPO-PEO; D011108:Polymers; D011409:Propylene Glycols; D020442:Poloxamer; D011092:Polyethylene Glycols; D004295:Dihydroxyphenylalanine