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Anti-HER2 Cationic Immunoemulsion as a Potential Targeted Drug Delivery System for the Treatment of Prostate Cancer

¹ Pharmaceutics Department, The School of Pharmacy; ² David R. Bloom Center for Pharmacy, The Hebrew University of Jerusalem; ³ Urology Department, Hadassah-Hebrew University Medical Center, Jerusalem, Israel; and ⁴ Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel

Requests for reprints: Simon Benita, Pharmaceutics Department, The School of Pharmacy, The Hebrew University of Jerusalem, P.O. Box 12065, Jerusalem 91120, Israel. Phone: 972-2-6758668; Fax: 972-2-6757140; E-mail: benita{at}cc.huji.ac.il.

Present management of metastatic prostate cancer, which includes hormonal therapy, chemotherapy, and radiotherapy, are frequently palliative. Taxanes, and specifically docetaxel, are being extensively investigated to improve the survival of metastatic prostate cancer patients. Although paclitaxel exhibits a wide spectrum of antitumor activity, its therapeutic application is limited, in part, due to its low water solubility that necessitates the use of Cremophor EL, which is known to induce hypersensitivity reactions. Therefore, the objective of this present study was to assess the efficiency of paclitaxel palmitate–loaded anti-HER2 immunoemulsions, a targeted drug delivery system based on cationic emulsion covalently linked to anti-HER2 monoclonal antibody (Herceptin), in a well-established in vivo pharmacologic model of metastatic prostate cancer that overexpresses the HER2 receptor. It was clearly noted that the cationic emulsion and immunoemulsion did not activate the complement compared with the commercial and paclitaxel palmitate hydroalcoholic formulations. In addition, 10 mg/kg of paclitaxel palmitate–loaded immunoemulsion once weekly over 3 weeks inhibits the tumor growth in severe combined immunodeficient mice much more than the cationic emulsion (P < 0.05) and the paclitaxel palmitate formulation (P < 0.01). The histopathologic analysis suggested a therapeutic improvement trend in favor of the immunoemulsion. However, there was no significant difference in antimetastatic activity between the emulsion and the immunoemulsion despite the affinity of the immunoemulsion towards the HER2 receptor. Although the tumor growth was not fully inhibited, the actual results are encouraging and may lead to an improved therapeutic strategy of metastatic prostate cancer treatment. [Cancer Res 2007;67(1):269–75]