title: SN-38 loaded polymeric micelles to enhance cancer therapy.
abstract: 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(ε-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 (IC(50)) 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, IC(50) 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.
authors.affiliation: Department of Biomedical Engineering, University of Alberta, Edmonton, AB, Canada.
authors.forename: Quanrong
authors.initials: Q
authors.lastname: Gu
authors.forename: James Z
authors.initials: JZ
authors.lastname: Xing
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Chuan
authors.initials: C
authors.lastname: He
authors.forename: Jie
authors.initials: J
authors.lastname: Chen
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000737:chemistry; D017209:Apoptosis / Q000187:drug effects; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D002470:Cell Survival / Q000187:drug effects; D004058:Diffusion; D006801:Humans; D000077146:Irinotecan; D008823:Micelles; D053769:Nanocapsules / Q000008:administration & dosage* / Q000737:chemistry*; D009374:Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism; D014407:Tumor Cells, Cultured
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D008823:Micelles; D053769:Nanocapsules; D000077146:Irinotecan; D002166:Camptothecin