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Aim: This study aims to assess the efficacy of free and niosomes-loaded paclitaxel combined with the anti-diabetic drug metformin. Methods: Paclitaxel was successfully encapsulated in all niosome formulations, using microfluidic mixing, with a maximum encapsulation efficiency of 11.9%. Results: The half maximal inhibitory concentration (IC 50 ) for free paclitaxel in T47D cells was significantly reduced from 0.2 to 0.048 mg/ml when combined with metformin 40 mg. The IC 50 of paclitaxel was significantly reduced when loaded in niosomes to less than 0.06 mg/ml alone or with metformin. Conclusion: Paclitaxel combination (free or loaded into niosomes) with metformin significantly improved the anticancer efficacy of paclitaxel, which can serve as a method to reduce the paclitaxel dose and its associated side effects.