Controlled application and scheduled removal of nanoparticle based chemotherapeutics (CARL) will reduce dose limiting adverse events in anticancer chemotherapy.

Clinical success of cancer chemotherapy is impaired by dose limiting toxicities. Nanoscale particle based drug delivery systems (DDS) like long circulating liposomes show improved toxicity profiles. Nevertheless, their unique pharmacokinetic properties lead to new dose limiting adverse events such as elevated skin toxicity. Though DDS accumulate in tumor tissue, only a very small fraction of the total dose reaches the target site. The overwhelming amount of a given dose is needed only to build up a diffusion gradient for effective accumulation at the target site. Due to the altered endothelial barrier, accumulation of DDS in tumor tissue is much faster than accumulation in other tissues, where dose limiting side effects occur. On the basis of these pharmakinetic data we hypothesize, that once accumulation in the tumor tissue is completed, rapid elimination of the DDS fraction still circulating in the plasma may diminish otherwise dose limiting toxicities.