Adhesive block copolymers for tissue repair and drug delivery

Triblock copolymers are of considerable interest in drug delivery because of their self-assembly properties and their ability to form hydrogels by warming from ambient to body temperature. In this paper, we describe a route for the conjugation of (3,4-dihydroxyphenyl)-L-alanine (DOPA) to the endgroups of PEO-PPO-PEO block copolymers. DOPA is an unusual amino acid found in mussel adhesive proteins (MAPS) that is believed to lend adhesive characteristics to these proteins. DOPA-containing proteins have been found to be mucoadhesive, so we surmised that incorporation of DOPA into block copolymers could improve the mucoadhesivity of these hydrogels. DOPA-modified Pluronics were freely soluble in cold water, and the copolymers aggregated into micelles at characteristic temperatures that depended on block copolymer composition and concentration in solution. Above a block copolymer concentration of approximately 20 wt%, solutions of DOPA-modified PEO-PPO-PEO block copolymers exhibited sol-gel transitions upon heating, and the characteristic temperature could be tailored between ∼23°C 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.