Reduction of tamoxifen resistance in human breast carcinomas by tamoxifen-containing liposomes in vivo.

摘要

We investigated whether it is possible to reduce anti-estrogen resistance using liposomally encapsulated tamoxifen in vivo. Small liposomal vesicles containing up to 5.1 mg tamoxifen/ml liposomal suspension, together with an alkylphospholipid to enhance the cellular uptake, were prepared and characterized. Mice transplanted with different tumor models were treated with tamoxifen liposomes administered i.p. or orally as a bolus dose of 50 mg/kg once a week or as a daily dose of 10 mg/kg/day, both during a 4-week period. After orally administered tamoxifen liposomes, tumor growth was significantly reduced for the 3366/tamoxifen (acquired resistance) and for the MCF-7 (inherent resistance) models to 47 and 16%, respectively (treated to control value of relative tumor volume). Intraperitoneal treatment with tamoxifen liposomes revealed similar results. Investigation of biodistribution revealed especially an accumulation of liposomal tamoxifen in MCF-7 tumors and livers of the treated mice. These liposomes had uterotrophic properties comparable to the dissolved compound. This study demonstrates for the first time that a liposomal formulation of tamoxifen was able to induce pharmacological effects and to improve the therapeutic efficacy in several anti-estrogen-resistant xenografts.