A model of binding of doxorubicin with heparin and enoxaparin

  • 1 Faculty of Fundamental Problems of Technology – Wroclaw University of Science and Technology, Poland

Abstract

Chemotherapy is one of the most successful methods of fighting with cancer, but like almost any kind of therapy, it has disadvantages such as severe side effects due to the high dose and/or unrestricted distribution within all body compartments. There have been numerous attempts to overcome these difficulties. The first option is to create a new active compound, what has shown to be very costly and, in many cases, ineffective. The other solution is to develop a new way to transport and release of existing drug in the organism using targeted drug delivery systems. Doxorubicin has been selected as a cytostatic substance that are already approved for medical use. The strategy is based on two features; entrapment of the active ingredient within the carrier by associating it with polymer and release it using external trigger guided by an imaging technique. The doxorubicin can be associated with heparin or enoxaparin. In order to implement the heparin/doxorubicin complex into the carrier structure, the thermodynamics of the aggregate formation need to be quantitatively described. The isothermal titration calorimetry has been used to extract the quantitative measures of its formation and stability, necessary for the designing both; pharmacological strategy and production process. To this end, the theoretical model of the binding has been developed and tested on well-defined experimental systems using heparins with different polymer lengths.

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