From Bench to Bedside—An Example of an In Situ Hydrogel in In Vivo Applications - In-Situ Gelling Polymers: For Biomedical Applications - page 216

Fig. 2 Comparison of paclitaxel distribution between human and rat brain 30 days after
implantation. a Paclitaxel distribution in rat (right panel) and human (left panel) brain obtained when
the solubility of paclitaxel in water is taken as the limiting factor for drug release form the polymer
matrix from a 7 % filled cavity. b Paclitaxel distribution in brain tissue assuming sink conditions in the
brain from a 7 % filled cavity. Based on the assumptions used in the simulation drug penetration dis-
tances can differ in about one order of magnitude. Only concentrations above the minimum effective
concentration have been displayed to visualize effective therapeutic distances. The convection term in
the diffusion-reaction equation has been left out because the focus of this data is the amount of drug
remaining in the polymer matrix due to the slow diffusion of paclitaxel and the difference in pen-
etration scale between rat and human brains. Concentrations are given in mol/m 3 . Reproduced from
Torres et al. [ 14 ]
Though, simulations assuming sink conditions increases the effective therapeu-
tic distances, it is inaccurate to assume sink conditions in the brain tissue (Fig. 2 b).
Nevertheless the study managed to establish that the penetration pattern of pacli-
taxel was similar to Gliadel ® wafers, with paclitaxel maintaining effective con-
centrations for more than 30 days where as Gliadel ® wafers could do so only for
4 days. They also reported that the convention in the brain tissue could prevent the
formation of a stable drug concentration gradient.
An attempt was made to do the phase 1 and 2 dose escalation study clinical
trials on subjects with recurrent glioma in a Protherics sponsored study in 2007.
Though the predicted completion of study was 2010, it was terminated citing pro-
fessional reasons.