Macromolecular Carriers for Methotrexate and Ferrocene in Cancer Chemotherapy

Abstract

Several drug-carrier polymers were synthesized in this program, including polyaspartamides, ester-amine condensation polymers, and polyamidoamines (PAAs). Functionalized polyaspartamides were obtained in 46–73% yield by an aminolytic ring-opening process resulting from the nucleophilic attack of a number of selected amines on polysuccinimide, which in turn was obtained by a high-temperature polycondensation reaction in the presence of phosphoric acid. These polyaspartamides were characterized by inherent viscosities in the range of 8–26 mL g⁻¹. The ester-amine polymers were obtained in 42–71% yield by base-catalyzed polycondensation reactions under controlled conditions of temperature, in DMSO, so as to ensure the incorporation and integrity of unprotected hydroxyl functional groups in the polymer’s main chain. These polymers were characterized by inherent viscosities in the range of 10–13 mL g⁻¹. PAAs were synthesized by the addition of amine nucleophiles across the double bonds of methylene bisacrylamide (Michael-type addition), under carefully controlled experimental conditions to obtain both amide and secondary amine functions in the water-soluble polymeric main chain. They were obtained in 16–29% yield and characterized by inherent viscosities in the range of 20–26 mL g⁻¹. These three types of polymers are perfectly water-soluble polymeric products which are purified by dialysis (12,000 molecular mass cut-off) and freeze-drying. They are of interest as macromolecular carriers for pharmaceuticals and biologically active agents.