Synthesis and characterization of degradable anhydride-co-imide terpolymers containing trimellitylimido-L-tyrosine: Novel polymers for drug delivery

The goal of this work is to synthesize a polymer specifically designed to deliver vaccine antigens. To accomplish this goal, a series of anhydride-co-imide terpolymers based on trimellitylimido-L-tyrosine (TMA-Tyr), sebacic acid (SA), and 1,3-bis(carboxyphenoxy)propane (CPP) was synthesized by melt condensation polymerization. It is desirable to incorporate tyrosine into the backbone of the polymer system due to its inherent ability to enhance the immune response to vaccine antigens. CPP and SA were copolymerized with the tyrosine derivative, TMA-Tyr, in order to develop a polymer with suitable material properties for drug delivery (e.g., high molecular weight, amorphous, and good solubility in low-boiling organic solvents), as well as to provide a series of polymers capable of a wide range of degradation and antigen release properties. To our knowledge, this paper represents the first report of the synthesis and characterization of terpolyanhydrides designed specifically to deliver drugs such as vaccine antigens. A systematic series of studies was performed to evaluate and optimize the influence of monomer ratio, reaction time and temperature, reaction catalysts, and catalyst concentration on polymer molecular weight, percent TMA-Tyr incorporation, and crystallinity. Terpolymers were synthesized with weight-average molecular weights in excess of 80 000 by using heterogenic catalysts and highly purified monomers with low degrees of oligomerization. In addition, the terpolymers had no crystalline regions, the only exception being polymers with >60% SA in their backbone. Monomers and polymers were characterized by ¹H NMR and IR spectroscopy, elemental analysis, thermal transition temperature analysis, and gel permeation chromatography. The stability of these polymers in the solid state and in chloroform at various temperatures is also reported.