Investigating the rheological behavior of Poloxamer–chitosan thermogel for in situ drug delivery of doxorubicin in breast cancer treatment: designed by response surface method (RSM)

Abstract

This research investigates the rheological behavior of the Poloxamer–chitosan thermogel system for the release of doxorubicin, which is a chemotherapy agent. To design the experiment, the response surface method was used to optimize the formula and investigate the mutual effects of the variables on the rheological properties of the system. In this experimental design, Poloxamer as a thermogel matrix (15–20%) and chitosan biopolymer as an additive (0.1–0.3%) were used and the pH of the test environment was determined in the range of 2.0–7.5. The results showed that the rheological behavior of the Poloxamer–chitosan combination has the best fit according to the Herschel–Bulkley model with a correlation coefficient of 100%. Also, adding chitosan to Poloxamer decreased the gelation temperature and gelation time. The results showed that the concentration of Poloxamer and chitosan as well as system temperature have a significant effect on the rheological behavior of thermogel. The optimized formula showed favorable rheological properties including high viscosity and appropriate degradation rate. The study showed the sustained release of the drug in the in vitro environment of the thermogel system during 144 h. The kinetics of the drug's release were also studied based on zero-order, first-order, Higuchi, and Korsmeyer–Peppas models. It was found that the Higuchi (R² = 0.9888) and Korsmeyer–Peppas (R² = 0.9851) models are the best models for the prediction of release kinetics of doxorubicin. Therefore, the design of the Poloxamer–chitosan thermogel system has the potential to be used as an in situ drug delivery system for doxorubicin.