Intralymphatic delivery of platinum-based chemotherapeutics is possible: an experimental study

Abstract

The results of this study demonstrate that intralymphatic delivery of cisplatinum, carboplatinum and oxaliplatin leads to higher drug concentrations in the retroperitoneal lymph nodes when compared with intravenous administration.

Indocyanine green nanoparticles undergo selective lymphatic uptake, distribution and retention and enable detailed mapping of lymph vessels, nodes and abnormalities

“…This concept, referred to as lymphatic drug insufficiency (LDI), was initially proposed and validated in our 2003 report [7], and recently confirmed in prospective studies in HIV patients that showed LDI of oral small-molecule antiretrovirals [8–10]. This is consistent with other reports in preclinical models and humans that showed the anti-cancer small molecules methotrexate [39], doxorubicin [40] and platinum-based chemotherapeutics [41] displayed limited lymphatic availability after IV and SC injection. This can result in negative clinical outcomes, particularly for antiviral therapy, as LDI in HIV patients on oral drug therapy has been associated with persistent HIV-1 RNA in LNs [8].…”

Docetaxel Accumulates in Lymphatic Circulation Following Subcutaneous Delivery Compared to Intravenous Delivery in Rats

“…Advancing the concept of locally delivered chemotherapeutics, several studies have also demonstrated lymphatic targeting of various formulations of locally delivered chemotherapeutics (27–37). Effectiveness of lymphatic penetration of these various formulations had been inferred from indirect lymphatic sampling methods to estimate the amount of product penetrating the lymphatics via lymph node tissue sampling, but have not been measured in lymph fluid prior to this study (8, 21, 38). Definitive lymph fluid sampling to assess lymphatic pharmacokinetics of locally delivered drug has occurred very rarely to date (10, 14, 39).…”

Lymphatic transport and lymph node targeting of methotrexate-conjugated PEGylated dendrimers are enhanced by reducing the length of the drug linker or masking interactions with the injection site

“…The lymphatic system is a major conduit for the growth and spread of disease including viral infection and cancer [1][2] . However, the distribution of small molecule therapeutics to the lymphatic system following intravenous (IV) administration is often low and many therapeutics administered for action within the lymphatic system have minimal lymphatic exposure [3][4][5][6][7] . Lymphatic targeting may be enhanced by interstitial (commonly subcutaneous, SC) delivery of macromolecular or nanoparticulate therapeutics, since the lymphatic vessels that drain the interstitium are more permeable to macromolecules than similarly located blood vessels [8][9][10] .…”