Evaluating the Accelerated Blood Clearance Phenomenon of PEGylated Nanoemulsions in Rats by Intraperitoneal Administration
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The accelerated blood clearance (ABC) phenomenon is induced by repeated intravenous injection of stealth polyethylene glycol (PEG) nanocarriers and appears as the alteration of the pharmacokinetics and biodistribution of the second administration. Nevertheless, there is no any report about the ABC phenomenon induced by intraperitoneal administration of PEGylated nanocarriers. In this study, we firstly observed whether the ABC phenomenon is induced with PEGylated nanoemulsion at the dose of 0.5~100 μmol phospholipid·kg−1 by intraperitoneal/intravenous injections in rats. The PEG (molecule weight, 2000)-modified nanoemulsions PE-B and PE in which fluorescence indicator dialkylcarbocyanines (DiR) is encapsulated by PE-B were prepared for this work. The pharmacokinetics of the first injected PE via veins or peritoneal cavity features different variation trends. Moreover, the tissue distributions (in vivo or in vitro) of the first injected PE by intraperitoneal injection reveals that the PE gains access to the whole lymphatic circulatory system. Furthermore, our results demonstrate that the ABC phenomenon can be induced by intraperitoneal administration PE-B and present obvious changes with varying PE-B concentration 0.5~100 μmol phospholipid·kg−1. Moreover, an interesting point is that the ABC phenomenon induced by intraperitoneal injected PE-B can be significantly inhibited by intraperitoneal pre-injection of distilled water. For understanding this issue clear, we studied the production of anti-PEG IgM and the characteristic morphologies of immune cells. We observed that the mast cells in peritoneal cavity exhibit rapid depletion in response to the intraperitoneal pre-injection of distilled water, while the anti-PEG IgM secretes at the same level.
KEY WORDSPEGylated emulsions ABC phenomenon intraperitoneal injection anti-PEG IgM mast cells
This research was aided financially by the National Natural Science Foundation of China (Grant Nos. 81072602, 81373334).
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