Abemaciclib is a Cyclin-dependent kinases (CDK) inhibitor which specifically targets CDK4/6 cell cycle pathway and have a potential anticancer activity. Unfortunately, it has low solubility and dissolution rate. In this study, Abemaciclib was loaded on chitosan polymer to enhance its solubility. Polymer nanoparticle and abemaciclib- polymer nanocomposites were prepared. Then, Minitab 18 software was used to design 18 run samples to study the effects of chitosan, Tripolyphosphate and pH as independent variables was studied on the loading efficiency and particle size (dependent variable). The response surface methodology (RSM) was also used to determine how the variables affected the response. The graphical analysis used surface plots, main effects plots, contour plots, and interaction graphs. The study includes F values, P values, variance inflation factors (VIFs), adjusted sums of square (Adj SSs), adjusted mean squares (Adj MSs) and square error of the coefficient (SE Coef). The carriers and loaded samples were also examined using the results of tests using Fourier transform infrared spectroscopy, X-ray diffraction, and scanning electron microscopy. Furthermore, the release of abemaciclib from nanocomposite was studied in vitro. The results revealed an ability to produce particle sizes ranging from (168-192) nm and loading efficiencies from (56.7-62.1). abemaciclib-chitosan nanocomposite may be used as an alternative drug delivery system for abemaciclib to increase the release time of abemaciclib to 1400 minutes.