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.: Home > International Journal of Medical Sciences > 2008 > Volume 5 Number 5 > Waldemar Waldeck1, Manfred Wiessler2, Volker Ehemann3, Ruediger Pipkorn4, Herbert Spring5, Juergen Debus6, Bernd Didinger6, Gabriele Mueller1, Joerg Langowski1, Klaus Braun2

TMZ-BioShuttle – a reformulated Temozolomide

Waldemar Waldeck1, Manfred Wiessler2, Volker Ehemann3, Ruediger Pipkorn4, Herbert Spring5, Juergen Debus6, Bernd Didinger6, Gabriele Mueller1, Joerg Langowski1, Klaus Braun2
1. German Cancer Research Center, Division of Biophysics of Macromolecules, INF 580, D-69120 Heidelberg, Germany 2. German Cancer Research Center, Dept. of Molecular Toxicology, INF 280, D-69120 Heidelberg, Germany 3. University of Heidelberg, Institute of Pathology, INF 220, D-69120 Heidelberg, Germany 4. German Cancer Research Center, Central Peptide Synthesis Unit, INF 580, D-69120 Heidelberg, Germany 5. German Cancer Research Center, Dept. of Structural Analysis of Gene Structure and Function, INF 280, D-69120 Heidelberg, Germany 6. University of Heidelberg, Dept. of Radiation Oncology, INF 400, D-69120 Heidelberg, Germany
Abstract :

There is a large number of effective cytotoxic drugs whose side effect profile, efficacy, and long-term use in man are well understood and documented over decades of use in clinical routine e.g. in the treatment of recurrent glioblastoma multiforme (GBM) and the hormone-refractory prostate cancer (HRPC). Both cancers are insensitive against most chemotherapeutic interventions; they have low response rates and poor prognoses. Some cytotoxic agents can be significantly improved by using modern technology of drug delivery or formulation. We succeeded to enhance the pharmacologic potency with simultaneous reduction of unwanted adverse reactions of the highly efficient chemotherapeutic temozolomide (TMZ) as an example. The TMZ connection to transporter molecules (TMZ-BioShuttle) resulted in a much higher pharmacological effect in glioma cell lines while using reduced doses. This permits the conclusion that a suitable chemistry could realize the ligation of pharmacologically active, but sensitive and highly unstable pharmaceutical ingredients without functional deprivation. The re-formulation of TMZ to TMZ-BioShuttle achieved a nearly 10-fold potential of the established pharmaceutic TMZ far beyond the treatment of brain tumors cells and results in an attractive reformulated drug with enhanced therapeutic index.

Keywords :
BioShuttle, Carrier Molecules; Drug Delivery; facilitated Transport; Glioblastoma multiforme (GBM); Reformulation, Temozolomide (TMZ)

Date Deposited : 28 Jul 2011 11:23

Last Modified : 28 Jul 2011 11:23

Official URL: http://www.medsci.org/archive

Volume 5, Number 5, - 2008 , ISSN 1449-1907

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