Process for the synthesis of a conjugate of hyaluronic acid and paclitaxel

A process for the prepaation and purification of a hyaluronic acid-paclitaxel (HA-paclitaxel) conjugate which comprises or consists of the following steps:

• a) activating in a solution of paclitaxel in an organic solvent, containing a 4-bromobutyric acid spacer/linker, of the carboxyl group of the 4-bromobutyric acid spacer/linker with an activating agent in the presence of a catalyst, thereby obtaining an intermediate of the HA-paclitaxel conjugate;
• b) crystallizing of the intermediate obtained from the previous step a), in an organic solvent, subsequently filtering and drying;
• c) adding the crystallized intermediate obtained in the previous step b) to a TBA (tetrabutylammonium) salt of HA in DMSO;
• d) purifying the HA-paclitaxel conjugate thus obtained which has an ester bond between the carboxyl of the HA polysaccharide and the spacer/linker, said spacer/linker being in turn bound by an ester bond through its carboxyl to the hydroxyl group at carbon C2′ of paclitaxel, by precipitation with an ethanol/water solution containing the NaBr salt, subsequently washing at least once in ethanol/water and further washing in ethanol, pre-drying at 40° C. and passage in a saturated chamber of water vapour at 40° C. and at atmospheric pressure, finally drying at 40° C. under vacuum.