Tyrosine-derived multiblock nonionic polymeric surfactants and drug carriers based on PEG: Synthesis, characterization, and solution behavior

Two types of polymeric systems for biomaterial applications were investigated. The first part of this work focuses on the synthesis, characterization, phase behavior and self-assembly in water of a new family of polymeric surfactants. The second part deals with the synthesis of a new a series of structurally related polymer-drug conjugates and the evaluation of their self-assembling properties in water.; Polymeric surfactants are important components of pharmaceutical formulations and drug delivery systems. In addition, their rheological properties are of interest in applications such as enhanced oil recovery and coating technology.; A new class of strictly alternating multiblock copolymers of poly(ethylene glycol) (PEG) and the tyrosine-derived diphenols desaminotyrosyl-tyrosine alkyl esters (DTR) was investigated. The distinctive feature of these polymers, referred to as poly(DTR-PEG ether)s, is the presence of multiple, regularly spaced hydrophobes in the pendent chain. By changing the molecular weight of PEG and the pendent chain length of the DTR units a series of materials with different phase behavior and self-assembling properties has been obtained. Phase behavior and self-assembly into micellar aggregates was investigated by light microscopy, modulated differential scanning calorimetry, light scattering, solubilization of a hydrophobic probe, and cryo-transmission electron spectroscopy. This investigation explored the surfactant behavior of poly(DTR-PEG ether)s and highlighted differences and similarities in their behavior in solution and at interphases as a function of composition.; The second part of this work is the synthesis and investigation of phase behavior of a series of structurally-related polymeric drug carriers. These materials reproduce the same structural motif as the polymeric surfactants, with the drug cis-4-hydroxy-L-proline alkyl ester ( c-Hyp) covalently attached as pendent chain in place of the alkyl chains. PEG blocks of different length have been incorporated in the polymer structures and different alkyl ester chains have been attached to the C-terminus of Hyp. The phase behavior and self-assembly of this series of polymer-drug conjugates was investigated similarly to the polymeric surfactants. It was found that the presence of alkyl ester groups at the Hyp C-terminus significantly affects their phase behavior, and that the length of these alkyl chains can be used to modify their self-assembling properties in aqueous solution.