Optimization of chitosan-based polyelectrolyte nanoparticles for gene delivery, using design of experiment: in vitro and in vivo study

Gene therapy is a novel approach for cancer treatment and investigation for suitable gene delivery systems is remarkable. Here, preparation of a polyelectrolyte complex containing polysaccharides: trimethyl chitosan (TMC) as the positive and hyaluronate (HA), dextran sulfate and alginate as the negative part was studied. The optimized nanoparticles (TMC: between 0.2 and 0.47 mg/ml, HA: 0.35 mg/ml (approximate to 131 nm, nearly full gene loading)) were obtained via primary screening followed by the D-optimal method. In vitro cellular study on the MCF7 cell line confirmed the non-toxicity and high cellular uptake (> 90%) of prepared nanoparticles. Notably, in vivo study indicated noticeable tumor uptake of nanoparticles while low accumulation in vital organs such as heart, liver and lungs. Moreover, although a qualitative variable was considered, the applied method restricted the number of runs by selecting spots from the spherical atmosphere. The prepared nano particles could be suggested as an efficient and safe delivery system for cancer gene delivery.

Automated summary

Gene therapy is a novel approach for cancer treatment, and the study of suitable gene delivery systems is crucial. The preparation of a polyelectrolyte complex containing polysaccharides was optimized and resulted in nanoparticles with high gene loading capacity. Both in vitro and in vivo studies confirmed the efficiency and safety of the prepared nanoparticles, suggesting their potential as a promising cancer gene delivery system.