AbstractIn this study, doxorubicin (DOX) loaded polymeric micelles (PMs) were synthesized based on biodegradable poly(ϵ‐caprolactone)‐poly(ethylene glycol)‐poly(ϵ‐caprolactone) (PCEC) triblock copolymers. So four parameters (shaking speed (rpm) X1, time of contact (hour) X2, amount of triethylamine (TEA) (μL) X3, DOX% X4) were optimized. Then by adding valspodar (PSC 833) or D‐α‐Tocopherol polyethylene glycol 1000 succinate (TPGS 1000) to the formulations DOX/PSC 833‐PMs or DOX/TPGS 1000‐PMs were prepared by a nanoprecipitation method. The synthesized micelles exhibited high drug‐loading encapsulation efficiency (>78.98 %), high stability, and pH‐dependent drug release. The results showed that the encapsulation efficiencies were not compromised by co‐encapsulation of two agents. Finally, it was observed that the association of both DOX and PSC 833 or both DOX and TPGS 1000 within a single micelle formulation elicited the most soluble DOX as compared to DOX loaded formulations (DOX‐PMs) while using a lower amount of polymer compared to separated micelle formulations.