Anti-HER2 cationic immunoemulsion as a potential targeted drug delivery system for the treatment of prostate cancer.
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.
Goldstein
Danny
D
Pharmaceutics Department, The School of Pharmacy, The Hebrew University of Jerusalem, Jerusalem 91120, Israel.
Gofrit
Ofer
O
Nyska
Abraham
A
Benita
Simon
S
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology / Q000494:pharmacology; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000737:chemistry; D045744:Cell Line, Tumor; D003167:Complement Activation / Q000187:drug effects / Q000276:immunology; D016503:Drug Delivery Systems / Q000379:methods*; D004655:Emulsions; D006801:Humans; D018796:Immunoconjugates / Q000008:administration & dosage* / Q000737:chemistry; D008297:Male; D051379:Mice; D017239:Paclitaxel / Q000008:administration & dosage* / Q000737:chemistry; D010168:Palmitates / Q000008:administration & dosage / Q000737:chemistry; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000276:immunology*; D000068878:Trastuzumab
D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000972:Antineoplastic Agents, Phytogenic; D004655:Emulsions; D018796:Immunoconjugates; D017239:Paclitaxel; D010168:Palmitates; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab