Optimizing Antitumor Efficacy and Adverse Effects of Pegylated Liposomal Doxorubicin by Scheduled Plasmapheresis: Impact of Timing and Dosing.

Background: Nanoscale drug delivery systems accumulate in solid tumors preferentially by the enhanced permeation and retention effect (EPR-effect). Nevertheless, only a miniscule fraction of a given dosage reaches the tumor, while >90% of the given drug ends up in otherwise healthy tissues, leading to the severe toxic reactions observed during chemotherapy. Once accumulation in the tumor has reached its maximum, extracorporeal elimination of circulating nanoparticles by plasmapheresis can diminish toxicities.

Accumulating nanoparticles by EPR: A route of no return.

Nanoparticle-based drug delivery to ease anticancer therapy relies primarily on the enhanced permeability and retention effect (EPR). The leaky vascular structure in tumors allows extravasation of nanoparticles, often termed passive targeting. Long term retention of nanoparticles is attributed to the lack of lymphatic drainage, and unidirectional extravasation has been implied.

Interference of phosphatidylcholines with in-vitro cell proliferation - no flock without black sheep.

According to early experiments with natural extracts, phosphatidylcholines (PCs) are widely considered essentially non-toxic. In addition to these physiological mixed-chain PCs, many different synthetic diacyl-PCs are currently available, but they have never been systematically evaluated for any interference with cell proliferation. We thus investigated the cell proliferation of several cell lines in the presence of various liposomes consisting of a single PC component and cholesterol.