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The clinical management of malignant diseases is often hampered by poor tissue uptake of drugs delivered to the site of action, as in the case of many tyrosine kinase inhibitors (TKIs). We hypothesized that a biomaterial delivery approach can increase the tissue distribution of imatinib (IM) and N-desmethyl imatinib (NDIM) to increase the local concentration of the drug. Cremophore EL and polyethylene glycol (PEG) were used to formulate submicron polymeric nanoparticles (NPs) to prolong the residence time of the encapsulated drug at the site of action. The ability to deliver the drug in NP form was evaluated in vitro. An orthotopic model of glioblastoma was established in nude mice to test the ability of the NPs to penetrate into the tumor parenchyma. The NPs were further evaluated in vitro and in vivo to determine whether they improved IM distribution and antitumor efficacy. The data showed that PEG-lactate-based NPs significantly improved the systemic and tumor distribution and prolonged the systemic residence time of IM and NDIM compared with the free drug or with Cremophore EL-based NPs. The improved tissue distribution of IM and NDIM in the tumor parenchyma translated into a significant antitumor activity in an orthotopic glioblastoma model in mice. A biomaterial delivery approach for TKIs can significantly improve their systemic and tumor distribution and their antitumor efficacy. This approach warrants further development for translation to the clinic. (1977), 14 Ill. App.3d 948, 303 N.E.2d 609. • 4 In the present case, the plaintiff was, to say the least, a qualified employee. Defendant's expert witnesses testified that there was no guarantee that the plaintiff would remain an employee. In fact, when plaintiff was asked how long he would remain in defendant's employ, he replied, "I don't know." 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There are a number of Adobe Certified Training Programs available System Requirements: OS: Windows XP/Vista/Windows 7/Windows 8 Processor: 2.0GHz Dual Core CPU Memory: 1 GB RAM Hard Disk: 200 MB Free Disk Space Display: 1024 x 768 Display Resolution Graphics: 256 MB Graphics Memory Network: Broadband Internet Connection ***SYSTEM REQUIREMENTS MAY VARY DEPENDING ON LOCATION*** 2. Important : To perform installation of the application, it is essential to have Windows XP, Vista or Windows 7. 3
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