Design, synthesis and evaluation of advanced polymeric taxane formulations

Hypersensitivity reaction upon intravenous administration of taxane medicines still severely affects the quality of life of patients in treatment with Taxol or Taxotere. Abraxane and Genexol-PM have been able to significantly lower or even exclude allergic reaction caused by surfactants such as Cremophor EL and polysorbate 80, used in Taxol and Taxotere, respectively. However, the manifested intrinsic systemic toxicity of chemotherapeutics including taxanes remains a major issue in conventional chemotherapy and shows that further exploration towards alternative formulations is required for pursuing more efficient and safer administration. Polymer-based drug formulations are attractive systems due to the chemical versatility and low-cost of polymeric carrier material compared to biotechnological carriers such as solubilizing proteins and monoclonal antibodies. As physical entrapment and chemical conjugation have already shown great promise in the development of second-generation polymeric chemotherapeutics, the overall aim of this thesis was to develop advanced polymeric taxane formulations based on these formulation strategies.

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