Paclitaxel, polymer formulation

Tanabe K, Serruys FW, Grube E, et al. TAXUS III Trial instent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation 2003 107(4)559-564. 

The polymer formulations containing anticancer agents (paclitaxel and cis-platin) were evaluated in vivo in heterotrophic (mouse bladder tumor) and orphotrophic (rat prostate cancer) models. Single administration of polymer-pactlitaxel formulation intratumorally in a mouse bladder tumor model increased the survival rate of the animals compared to untreated animals and to animals treated with paclitaxel dispersion (conventional administration method) (27). The optimal load of paclitaxel in the polymer was established as 10% w/w. Mice treated with this formulation showed median survival rate (MSR) of... 

The polymer-paclitaxel formulation was also evaluated for treatment of orthotopic prostate cancer (28). Treatment with the polymer formulation of paclitaxel (single injection of 200 pi polymer formulation with 10% w/w load) increased the survival rate of the rats. Rats treated with parental formulation of paclitaxel died 25 days post tumor cells inoculation. Only one rat in the polymer-paclitaxel group died three weeks post tumor cell inoculation, while all the remaining rats survived until the end point of the experiment (35 days). The control animals also developed lymph node metastases. No metastases were found in polymer-paclitaxel treated rats. The treatment with polymer-paclitaxel formulation reduced the prostate volume of the rats from 14.8 cm (untreated animals) to 0.862 cm while the volume of healthy prostate gland injected with 200 pi of polymer is about 0.4 cm The polymeric formulation released paclitaxel into local tumor tissues and induced necrosis and reduction of the tumor mass, while prolonging lifespan in an orthotopic prostate cancer rat model. 

Poor water solubility of drugs and new chemical entities presents major challenges in the development of clinically useful formulations. Of the various approaches used for enhancing the solubility of poorly soluble drugs, polymeric delivery systems have been used effectively. Paclitaxel has been used as a model hydrophobic drug to show the effectiveness of solubility-enhancing properties of various polymeric delivery systems. Recently, hydrotropic polymers were developed based... 

Levy-Nissenbaum, E., Khan, W., Pawar, R.P., Tabakman, R., Naftali, E., Winkler, I., Kaufman, O., Klapper, L., Domb, A.J., 2012. Pharmacokinetic and efficacy study of cisplatin and paclitaxel formulated in a new injectable poly(sebacic-co-ricinoIeic acid) polymer. European Journal of Pharmaceutics and Biopharmaceutics 82, 85—93. 

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