SN-38 loaded polymeric micelles to enhance cancer therapy

摘要

7-Ethyl-10-hydroxycamptothecin (SN-38) loaded poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (Pluronic F-108) and poly(ethylene glycol)-block-poly("-caprolactone) (PEG-b-PCL) nanoparticles were successfully prepared by a modified film hydration method and characterized by scanning electric microscopy (SEM), transmission electron microscopy (TEM), atomic force microscopy (AFM) and dynamic light scattering (DLS). Satisfactory drug loading of 20.73 ± 0.66% and a high encapsulation efficiency of 83:83 ± 1:32% were achieved. The SN-38 nanoparticles (SN-38 NPs) can completely disperse into a phosphate buffered saline (PBS) medium to produce a clear aqueous suspension that remains stable for up to three days. Total drug releases were 67.91% and 91.09% after 24 h in a PBS or fetal bovine serum (FBS) medium. Half maximal inhibitory concentration (IC50) tests of SN-38 and SN-38 NPs on A549 lung cells produced results of 200.0±14.9 ng ml ~(-1) and 80.0±4.6 ng ml ~(-1), respectively. Similarly, IC50 tests of SN-38 and SN-38 NPs on MCF-7 breast cells yielded results of 16.0 ± 0.7 ng ml ~(-1) and 8.0 ± 0.5 ng ml ~(-1), respectively. These in vitro IC _(50) studies show significant (p < 0.01) enhancement of the SN-38 NP drug efficiency in killing cancer cells in comparison to the free drug SN-38 control. All the materials used for this nanoformulation are approved by the US FDA, with the virtue of extremely low toxicity to normal cells.