A Doxorubicin Loaded Chitosan-poloxamer Implant for the Treatment of Breast Cancer

Breast cancer is a serious concern for many women worldwide. Drug-loaded implants have shown several benefits over systemic administrations. To provide anti-cancer drugs with controlled release and reduced systemic toxicity, biodegradable implants have attracted a lot of attention. In the present study, we aimed to design and optimize a doxorubicin-loaded chitosan-poloxamer implant for breast cancer treatment. Utilizing Box-Behnken Design and a Quality-by-Design (QbD) methodology, the implant was prepared with chitosan (X1), poloxamer 407 concentration (X2), and stirring time (X3) as the independent variables. It was characterized for its gelation time, pH, rheology, and morphology, and evaluated based on drug release profile, cytotoxicity activities, anti-inflammatory potential, cellular uptake, and anti-inflammatory and pharmacokinetics to ensure their therapeutic outcomes. The results revealed that the prepared formulation showed a gelation time of 26 ± 0.2 s with a viscosity of 8312.6 ± 114.2 cPs at 37 °C. The developed formulation showed better cytotoxic activity in MCF-7 cell lines compared to the free drug solution. It demonstrated reduced levels of pro-inflammatory cytokines in RAW 264.7 macrophages. Further, the prepared implant increases the intracellular accumulation of DOX in the MCF-7 cells. The pharmacokinetic investigations depicted an increase in and a decrease in AUC of the developed formulation resulting in prolonged drug release and there could be a lower drug concentration in the bloodstream than for the free drug. Therefore, the developed implant may offer a viable option for breast cancer treatment.