PEGylated squalenoyl-gemcitabine nanoparticles for the treatment of glioblastoma
| Autor: | Alice Gaudin, Jennifer K. Saucier-Sawyer, Amanda King, Eric Song, Didier Desmaële, W. Mark Saltzman, Patrick Couvreur, Ranjit S. Bindra |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Squalene
Radiosensitizer Antimetabolites Antineoplastic Materials science Cell Survival Biophysics Nanoparticle Bioengineering 02 engineering and technology Pharmacology Deoxycytidine Nanocapsules Article Polyethylene Glycols Biomaterials Diffusion 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Cell Line Tumor PEG ratio medicine Distribution (pharmacology) Animals Humans Dose-Response Relationship Drug Brain Neoplasms technology industry and agriculture 021001 nanoscience & nanotechnology Gemcitabine Molecular Imaging Rats Treatment Outcome chemistry Absorption Physicochemical Mechanics of Materials 030220 oncology & carcinogenesis Ceramics and Composites 0210 nano-technology Glioblastoma Nucleoside medicine.drug |
| Zdroj: | Biomaterials. 105 |
| ISSN: | 1878-5905 |
| Popis: | New treatments for glioblastoma multiforme (GBM) are desperately needed, as GBM prognosis remains poor, mainly due to treatment resistance, poor distribution of therapeutics in the tumor tissue, and fast metabolism of chemotherapeutic drugs in the brain extracellular space. Convection-enhanced delivery (CED) of nanoparticles (NPs) has been shown to improve the delivery of chemotherapeutic drugs to the tumor bed, providing sustained release, and enhancing survival of animals with intracranial tumors. Here we administered gemcitabine, a nucleoside analog used as a first line treatment for a wide variety of extracranial solid tumors, within squalene-based NPs using CED, to overcome the above-mentioned challenges of GBM treatment. Small percentages of poly(ethylene) glycol (PEG) dramatically enhanced the distribution of squalene-gemcitabine nanoparticles (SQ-Gem NPs) in healthy animals and tumor-bearing animals after administration by CED. When tested in an orthotopic model of GBM, SQ-Gem-PEG NPs demonstrated significantly improved therapeutic efficacy compared to free gemcitabine, both as a chemotherapeutic drug and as a radiosensitizer. Furthermore, MR contrast agents were incorporated into the SQ-Gem-PEG NP formulation, providing a way to non-invasively track the NPs during infusion. |
| Databáze: | OpenAIRE |
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