Polymer drug conjugates with chemotherapeutics may significantly altering of properties of the drugs (e.g. increase the half life, stability etc.). The conjugate of paclitaxel (TXL) with poly-L-glutamic acid (PGA) was synthesised. This conjugate is better soluble in water than paclitaxel, which is a big advantage for therapeutic purposes. The conjugate structure and paclitaxel content were checked using ¹H NMR analysis. Next, we used the synthesised conjugate for anticancer therapy of mice bearing B16(F10) melanoma tumours. When the tumours reached ca. 100 mm³, the mice received a single dose of drug conjugate (equivalent of 50 mg paclitaxel/kg of body mass), intratumorally or intravenouosly (i.v.). Despite the fact that tumor growth inhibition in the treated groups was rather small, mice receiving the conjugate by iv. route showed extended lifespan compared to those receiving the drug intratumorally or the control group. We also checked the usefulness of this conjugate in therapy of lung metastases in mice. We observed decreased size and number of melanoma lung metastases after a single dose of PGA-TXL.

The project was supported by the Ministry of Science and Higher Education, grant PBZ-KBN-091/P05/2003

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