QbD-based co-loading of paclitaxel and imatinib mesylate by protamine-coated PLGA nanoparticles effective on breast cancer cells

Aim: Paclitaxel and imatinib mesylate are drugs used in the treatment of breast cancer. Conventional drug-delivery systems have limitations in the effective treatment of breast cancer using the drugs. Materials & methods: Combination index studies were used to identify the optimum ratio of both drugs showing maximum synergistic effect. Using a systematic quality-by-design approach, protamine-coated PLGA nanoparticles co-loaded with paclitaxel and imatinib mesylate were formulated. Further characterization and cell line evaluations were performed. Results: Encapsulation efficiency obtained was 92.54% for paclitaxel and 75.12% for imatinib mesylate. A sustained (24 h) and controlled zero-order drug release was obtained. Conclusion: Formulated nanoparticles had a low IC50 value and enhanced cellular uptake. Paclitaxel and imatinib (PXL and IMA) show synergistic efficacy against the MCF-7 cell line of breast cancer. PXL and IMA in the ratio of 4:1 show maximum effect and lowest combination index (CI). Quality-by-design methodology led to optimization and systematic formulation of coloaded protamine-coated PLGA nanoparticles. Protamine decreased the initial burst release of the formulations. A sustained zero-order drug release was obtained for both the formulations. Protamine coating was clearly visible on images using transmission electron microscopy analysis. Significant reduction in IC50 values showing increased cytotoxicity was observed. Roughly 30-fold increase in cellular uptake was obtained as compared with free drugs.