Topotecan and doxorubicin combination to treat recurrent ovarian cancer: the influence of drug exposure time and delivery systems to achieve optimum therapeutic activity.

Purpose: To provide proof-of-concept data to support use of Doxil-liposomal topotecan (Topophore C) combinations to treat ovarian cancer.

Experimental Design: ES-2, OVCAR-3, and SKOV-3 ovarian cancer cell lines were treated with doxorubicin-topotecan combinations by exposing the cells to drugs from 1 to 72 hours. Pharmacokinetic analysis was conducted following administration of liposomal formulations of these drugs alone and in combination.

Topophore C: a liposomal nanoparticle formulation of topotecan for treatment of ovarian cancer.

We have recently developed a liposomal nanoparticle (LNP) formulation of irinotecan based on loading method that involves formation of a complex between copper and the water soluble camptothecin. The loading methodology developed for irinotecan was evaluated to develop a LNP topotecan formulation (referred to herein as Topophore C) and test its activity in pre-clinical model of ovarian carcinoma. Topotecan was encapsulated into preformed liposomes containing 300 mM copper sulfate and the divalent metal ionophore A23187.

The role of the transition metal copper and the ionophore A23187 in the development of Irinophore C™.

Purpose: A liposomal irinotecan formulation referred to as Irinophore C relies on the ability of copper to complex irinotecan within the liposome. It is currently being evaluated for critical drug-loading parameters. Studies presented here were designed to determine the optimum copper concentration required for the effective encapsulation and retention of irinotecan into liposomes.

Role of phospholipid transfer protein on the plasma distribution of amphotericin B following the incubation of different amphotericin B formulations.

Purpose: The purpose of this study was to investigate the role of phospholipid transfer protein (PLTP) on the plasma distribution of amphotericin B (AmpB) following incubation with different AmpB formulations in human plasmas with varying lipid profiles.

Methods: In a first set of experiments, plasma distribution profiles of AmpB were determined following the incubation of Fungizone and lipid-based formulations (Abelcet and AmBisome) at a concentration of 20 microg AmpB/mL for 5-120 min at 37 degrees C in the plasma obtained from six different individuals (total cholesterol concentrations range between 62 and 332 mg/dL). In a second set of experiments, Abelcet, and AmBisome at a concentration of 20 microg AmpB/mL were incubated for 5 min at 37 degrees C in human plasma (total cholesterol = 163 mg/dL) that had been pretreated with an antibody raised up against PLTP (1:400 v/v dilution from stock solution) for 20 min at 37 degrees C.

Unidirectional inhibition of lipid transfer protein I-mediated transfer of cholesteryl esters between high-density and low-density lipoproteins by amphotericin B lipid complex.

Purpose: The purpose of this study was to determine whether Fungizone or amphotericin B lipid complex (ABLC; ABELCET) affects the transfer of cholesteryl ester (CE) by lipid transfer protein I (LTP I; also known as cholesteryl ester transfer protein) between HDL and LDL (bidirectional transfer HDL to LDL and LDL to HDL).

Methods: Increasing concentrations of either Fungizone or ABELCET (1.25-12.