Effect of poly(allylamine) molecular weight on drug loading and release abilities of nano-aggregates for potential in cancer nanomedicine

Poly(allylamine) graft polymers have been shown to hold potential as drug delivery vehicles and complexation agents for biological molecules such as insulin. The nanoparticles formed upon aggregation or complexation allow for enhanced cellular trafficking resulting in enhanced efficacy. Multiple reports have shown the ease of synthesis and reliability of these graft polymers, however, little investigation into the effect of the molecular weight of the homopolymer poly(allylamine) has been carried out. In this work we synthesized a range of oxadiazole grafted poly(allylamine) derivatives of varied molecular weight (15, 17.5, 120 & 900 kDa) set at a 5% polymer:oxadiazole mole grafting. The effect of molecular weight on the size, critical aggregation concentration and drug loading / release was evaluated in model drugs before loading the optimal formulation with doxorubicin and carrying out a preliminary cytotoxicity study. In line with other cationic polymers, the larger poly(allylamine) amphiphilic derivatives resulted in greater drug loading, however, the particle size increased whilst drug loading dramatically decreased, which for cancer nanomedicine could be a barrier for pharmaceutical use.