Polyanhydride modified unsaturated polyesters as injectable drug carriers: Synthesis and antitumor efficacy in Sarcoma-180 mice bearing tumor

New polyanhydride modified unsaturated polyesters, poly(dodecanedioic acid-tetradecanedioic acid) [P(DDDA-TA)] modified poly(fumaric acid-glycol) [P(FA-GLY)] copolymers, were prepared by melt polycondensation with corresponding polyanhydride and unsaturated polyester synthesized beforehand. The polyanhydride was characterized by FT-IR, gel permeation chromatography (GPC), differential scanning calorimetry (DSC) and thermal gravimetric analysis (TGA), the liquid poly(fumaric acid-glycol) [P(FA-GLY)] and polyanhydride modified unsaturated polyesters were characterized by FT-IR, gel permeation chromatography (GPC) and viscosity of the polymers was measured with a Ubbelohde viscometer. In vitro studies showed that some of the copolymers are degradable in phosphate buffer at 37 °C and have properly drug release rate as drug carriers. The biocompatibility of P(DDDA-TA)-P(FA-GLY) copolymers under mice skin was also evaluated; macroscopic observation and microscopic analysis demonstrated that the copolymer is biocompatible and well tolerated in vivo. Antitumor efficacy of P(DDDA-TA) [molar ratio MDDDA:MTA = 1.0:1.0, 20% weight ratio in polyanhydride modified unsaturated polyester]-P(FA-GLY) [molar ratio MFA:MGLY = 1.0:1.1] containing 5% adriamycin hydrochloride (ADM) in Sarcoma-180 mice bearing tumor exhibited increased volume doubling time (VDT) (21 ± 1.5 days) compared to plain subcutaneous injection of adriamycin hydrochloride (ADM) (7 ± 1.0 days), and the antitumor efficacy of injected preparation of P(DDDA-TA)-P(FA-GLY)-ADM inside tumor twice intervene 16 days exhibited an especially increased cytotoxic effect as revealed by increased volume doubling time (VDT) (32 ± 2.5 days). The studies suggested that P(DDDA-TA)-P(FA-GLY) copolymers as an effective and injectable carrier of antineoplastic drug like adriamycin hydrochloride have a very good foreground in treatment of noumenon tumor.