Edelfosine (ET) is a potent antitumor agent but causes severe side effects that have limited its use in clinical
practice. For this reason, nanoencapsulation in lipid nanoparticles (LNs) is advantageous as it protects from ET
side-effects. Interestingly, previous studies showed the efficacy of LNs containing ET in various types of tumor. In
this paper, biodistribution studies of nanoencapsulated ET, administered by three routes (oral, intravenous (IV)
and intraperitoneal (IP)), were tested in order to select the optimal route of administration. To do this, ET-LNs
were labeled with Technetium-99 m (99mTc) and administered by the oral, IV and IP route in mice. IV admin-
istration of the radiolabeled LNs led to fast elimination from the blood circulation and increased accumulation in
reticulo-endothelial (RES) organs, while their oral administration could not provide any evidence on their bio-
distribution since large radiocomplexes were formed in the presence of gastrointestinal fluids. However, when
the LNs were administered by the IP route they could access the systemic circulation and provided more constant
blood ET-LN levels compared to the IV route. These findings suggest that the IP route can be used to sustain the
level of drug in the blood and avoid accumulation in RES organs
