The goal of the current study is to develop a chitosan alginate nanoparticle system encapsulating the model drug, simvastatin (SIM-CA-NP) using a novel polyelectrolytic complexation method. The formulation was optimized using the central composite design by considering the concentrations of chitosan and alginate at five different levels (coded as +1.414, +1, 0, -1, and -1.414) in achieving minimum particle size (PS-Y1) and maximum entrapment efficiency (EE-Y2). A total of 13 runs were formulated (as projected by the Design-Expert software) and evaluated accordingly for the selected responses. On basis of the desirability approach (D = 0.880), a formulation containing 0.258 g of chitosan and 0.353 g of alginate could fulfill the prerequisites of optimum formulation in achieving 142.56 nm of PS and 75.18% EE. Optimized formulation (O-SIM-CAN) was further evaluated for PS and EE to compare with the theoretical results, and relative error was found to be within the acceptable limits, thus confirming the accuracy of the selected design. SIM release from O-SIM-CAN was retarded significantly even beyond 96 h, due to the encapsulation in chitosan alginate carriers. The cell viability study and Caspase-3 enzyme assay showed a notable difference in contrast to that of plain SIM and control group. All these stated results confirm that the alginate-chitosan nanoparticulate system enhanced the anti-proliferative activity of SIM.
Keywords: alginate; caspase-3-enzyme assay; central composite design; chitosan; simvastatin.