BB 03. Unique Porcine Model Of Fatal Side Effects Of Nanodrugs/Nanocarriers


D. Csukás, R. Urbanics, J. Szebeni, A Ferencz, G. Szabó, J. Sándor, L. Seres, D. Fehér, G. Wéber

Chair(s): Frank Dor, Thomas Theologou, Fatih Can, Osman Yuksel & Alexander Schachtrupp

12:10 - 12:20h at Erszebet Room (A)

Categories: B.Braun Award

Session: B.Braun Award Session


Background:
Many of commonly used, state-of-art drugs are built up of complex molecular structures of nano- range. Their specific hypersensitive reaction is called complement activation-related pseudoallergy (CARPA). Symptoms appear abruptly, and may lead to lethal consequences in some patients. Beside the complement activation it is highly probable that in the background of this reaction the vasoactive substance releasing pulmonary intravascular macrophages (PIM cells) play significant role. Our aim is to describe the porcine CARPA reaction model.

Material and Methods:
Experiments were performed on anesthetized domestic pigs (n=15). In the testing procedure Doxil (liposomal doxorubicin), some other nanocarriers, and Zymosan (direct complement system activator) were used. A Swan-Ganz catheter was introduced into the pulmonary artery for pressure measurement (PAP). The ECG, heart rate, and systemic arterial pressure were also continuously monitored. Blood cell count analyses and tromboxane-B2 (TxB2) tests were performed.

Result:
According to our results PAP raised immediately to a multiple level after i.v. application of certain nanocarriers. Tachycardia and decrease of peripheral blood pressure were observed too. Moreover, hyperaemic skin changes (flush) or transitional apnoe appeared. Blood tests revealed both leuko-, and thrombocytopenia, and increased level of TxB2.

Conclusion:
Our porcine model showed high sensitivity and specificity about the CARPA reactions. The typical appearance of the acute symptoms is similar to the human medical observations. Further experiments are necessary to expose the cellular background, especially the function of PIM cells.