Aliphatic polyamides prepared by ester-amine polycondensation as potential drug carrier polymers

Aliphatic polyamides of interest as macromolecular drug carriers are synthesized by base-catalyzed polycondensation of aliphatic diesters with diamines. The reactions are conducted in the presence of anhydrous sodium carbonate at temperatures ranging from ambient to 65°C, initially in the undilute state. The addition of aprotic solvent at a later stage serves to maintain sufficiently low viscosity for proper homogenization. The comonomers, diethyl 3,6,9-trioxaundecanedioate and 4,7,10-trioxa-1,13-tridecanediamine, copolymerize to form polymer 1, a straight-chain polyamide devoid of specific functionality. Use of diethyl tartrate in lieu of the aforementioned diester leads to polyamide 2 possessing hydroxyl side groups. Other experiments in which diamines incorporating additional (secondary) amino groups are employed afford polyamides 3–8 containing such secondary amine functions as main-chain constituents. The water-soluble target polymers are crudely fractionated by aqueous dialysis (12000–14000 molecular mass cut-off) and collected by freeze-drying in yields of 20 to 40%. The low-yield range has been accepted in this investigation as the price to be paid for the realization of linear polyamide structures in accordance with compositional expectations, a requirement vital for the proper functioning of the polymers as drug carriers. The practicability of drug binding (conjugating) is exemplified by the coupling of ferrocene as a drug model to polyamide 5 via amide linkage. The water-soluble conjugate 5-Fc features an iron content corresponding to one ferrocene group in the repeat unit. © 1999 John Wiley & Sons, Inc. J Appl Polym Sci 73: 2143–2150, 1999