Intratumoral Delivery of Paclitaxel for Treatment of Orthotopic Prostate Cancer SERGEY SHIKANOV, 1 ARIELLA SHIKANOV, 2 OFER GOFRIT, 1 ABRAHAM NYSKA, 3 BENJAMIN CORN, 4 ABRAHAM J. DOMB 2 1 Department of Urology, Hadassah Medical Center, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel 2 Department of Medicinal Chemistry and Natural Products, School of Pharmacy Faculty of Medicine, The Hebrew University of Jerusalem, 91120 Jerusalem, Israel 3 Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel 4 Institute of Radiotherapy, Tel-Aviv Sourasky Medical Center, Tel-Aviv, Israel Received 28 December 2007; revised 23 May 2008; accepted 9 June 2008 Published online 25 July 2008 in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jps.21492 ABSTRACT: Locally recurrent prostate cancer can lead to significant morbidity, meta- stasis, and even death. The objective of this study was to evaluate the efficacy of an injectable polymeric paste formulation containing paclitaxel against orthotopic prostate tumor in rats. The Dunning R-3327 rat prostate adenocarcinoma is experimental tumor model used to study tumor progression. The polymer loaded with paclitaxel was injected into the tumor bearing prostate glands of the rats 3 days after tumor cell inoculation. In control untreated rats, tumor volume reached 14 cm 3 after 25 days, while in rats treated with intratumoral injection of polymer/paclitaxel formulation the prostate volume with the tumor was only 0.9 cm 3 , 35 days posttumor cells inoculation. In the group treated with intratumoral injection of paclitaxel suspension, the tumor volume was 6.6 cm 3 , and in the group treated with intraperitonial (IP) paclitaxel formulation, the tumor volume reached 13.9 cm 3 25 days posttumor cells inoculation. No metastases were found in rats treated intratumorally with 200 mL of polymer/paclitaxel formulation, while rats in other treatment groups developed metastases in the lungs and lymph nodes. The results of this study indicated that a site-directed, injectable, controlled release formulation of paclitaxel is effective against localized prostate tumors and metastasis. ß 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:1005–1014, 2009 Keywords: biodegradable polymers; cancer chemotherapy; controlled release; in- jectables; polymeric drug delivery systems INTRODUCTION Many effective therapeutic options can be offered to a patient with organ confined prostate cancer, the most frequently employed are radical prosta- tectomy and external beam radiotherapy. Locally recurrent prostate cancer can lead to significant morbidity, metastasis, and death. The growing population of this kind of patients, some of them young and healthy, fuels the interest in salvage therapies. The results of salvage radical prosta- tectomy after radiotherapy, salvage radiotherapy after radical prostatectomy, and salvage cryother- apy are unsatisfactory, with cure rates of only 23–50%, and significant morbidity. 1,2 This re- ality justifies interest in novel therapies such as localized chemotherapy either alone or as an Leonyl Jacobson Chair of Medicinal Chemistry, affiliated with the Devid R. Bloom Center for Pharmacy and the Alex Grass Center for Synthesis and Drug Design at The Hebrew University of Jerusalem. Correspondence to: Abraham J. Domb (Telephone: 972-2- 6757573; Fax: 972-2-6757629; E-mail: avid@ekmd.huji.ac.il) Journal of Pharmaceutical Sciences, Vol. 98, 1005–1014 (2009) ß 2008 Wiley-Liss, Inc. and the American Pharmacists Association JOURNAL OF PHARMACEUTICAL SCIENCES, VOL. 98, NO. 3, MARCH 2009 1005