High-molecular-weight Polymers Containing Biodegradable Disulfide Bonds: Synthesis and In Vitro Verification of Intracellular Degradation

Abstract

The synthesis, physico-chemical behavior, and in vitro intracellular degradation of new biodegradable graft, diblock or multiblock polymer carriers that were designed to deliver bioactive compounds by passive tumor targeting were investigated. The graft polymer carriers consisted of the N-(2-hydroxypropyl)methacrylamide (HPMA) copolymer backbone grafted with a semitelechelic HPMA copolymer. The diblock polymer carriers were prepared by condensation of two semitelechelic HPMA copolymers. The multiblock polymer drug carrier was prepared by oxidative polycondensation of PEG-bis-cysteine. In all three carrier systems, the single polymers were linked via biodegradable disulfide bonds forming the graft, diblock or multiblock polymers. These polymers are potential polymer carriers for solid tumor-specific drug delivery with subsequent intracellular degradation to short polymer fragments that can be excreted by glomerular filtration. Prolonged blood circulation, accumulation in solid tumors, and drug release from these carriers have been reported. Here, degradation of the polymers in model buffer solutions mimicking intracellular environment as well as after incubation with EL4 T-cell lymphoma cancer cells were investigated. In both cases, degradation resulted in polymer fragments of molecular weight below the renal threshold.