Optimization of formulation and process of paclitaxel mPEG-PDLLA nanoparticles by Box-Behnken response surface methodology

LI Jin-ming; LI Rong-rong; TIAN Jing-zhen

Abstract：Objective: To optimize the formulation and process parameters of paclitaxel methoxy-poly (ethylene glycol)poly (D, L-lactide )copolymer (mPEG-PDLLA )nanoparticles. Methods: The nanoparticles were prepared by the high pressure microfluidization method. To optimize the formulation, mPEG-PDLLA concentration, sodium cholate hydrate concentration and the mass ratio of mPEG-PDLLA to paclitaxel were selected as independent variables, and entrapment efficiency and durg loading as response variables. To optimize the process, homogenization pressure, cycle numbers of homogenization and preparation temperature were selected as independent variables, and mean particle size as response variable. The formulation and process variables were optimized by Box-Behnken response surface methodology. The morphology, release characteristic in vitro and stability were investigated. Results: The optimal formulation and process parameters were as follows: the concentration of mPEG-PDLLA was 22. 4 mg·mL-1, the concentration of sodium cholate hydrate was 0. 2％, the mass ratio of mPEG-PDLLA to paclitaxel was 5∶1, the homogenization pressure was 109 MPa, the cycle numbers of homogenization was 6, the preparation temperature was 12. 5℃. The entrapment efficiency, the drug loading and mean particle size were (90. 21 ± 0. 99)％, (12. 58 ± 0. 50)％, and (115. 4 ± 5. 3)nm, respectively. The standard deviations were all less than 5％. The nanoparticles were spherical particles and had a sustained release property. The nanoparticles stored at (4 ± 2 )℃ for 3 months were stable. Conclusion: The Box-Behnken response surface methodology facilitates the optimization of formulation and process of paclitaxel mPEG-PDLLA nanoparticles.