Synthesis and Characterization of Self- Assembling Block Copolymers Containing Adhesive Moieties

Introduction Pluronics, a family of poly(ethylene oxide)-poly(propylene oxide)poly(ethylene oxide) (PEO-PPO-PEO) triblock copolymers, are of considerable interest in the biotechnological and pharmaceutical industry for their unique surfactant abilities, low toxicity, and minimal immune response.1 Aqueous solutions of Pluronic copolymers exhibit interesting temperatureinduced aggregation phenomena as a result of the hydrophobic nature of the PPO block. In some cases, gelation of concentrated Pluronic solutions occurs upon heating to temperatures at or just above ambient, a property which is potentially useful for medical drug delivery applications. For example, in-situ gelling materials are potentially useful as carriers for drug delivery to mucosal surfaces, i.e. the oral cavity and the respiratory, gastrointestinal, and reproductive tracts. The overall goal of this work is to synthesize new block copolymers that have the ability to form bioadhesive hydrogels in-situ. One strategy for enhancing the bioadhesive characteristics of polymers is to introduce biological moieties that are known to possess adhesive properties in nature. For example, it is known that marine mussels secrete unique adhesive proteins (mussel adhesive proteins, MAPs) that form strong moisture-resistant bonds to a variety of underwater surfaces.2 One interesting feature of MAPs is the presence of 3-(3,4-dihydroxyphenyl)-L-alanine (DOPA), an amino acid which is believed to be responsible for both adhesion and cross-linking characteristics of MAPs.2,3 The catechol form of DOPA is thought to be responsible for adhesion to surfaces, while the oxidized oquinone form is responsible for cross-linking of the MAPs.3 Recently, DOPA-containing synthetic polypeptides have been chemically synthesized by copolymerization of N-carboxyanhydride monomers of lysine and DOPA.4 The water soluble polypeptides were found to form gels in the presence of oxidizing agents, and adhesion to various substrates was observed. In this paper we describe the preparation of DOPAmodified Pluronics which have the ability to form polymer hydrogels by a thermally triggered self-assembly process.