The long-circulating effect of pegylated nanoparticles revisited via simultaneous monitoring of both the drug payloads and nanocarriers  

作　　者：Wufa Fan Haixia Peng Zhou Yu Luting Wang Haisheng He Yuhua Ma Jianping Qi Yi Lu Wei Wu 

机构地区：[1]Key Laboratory of Smart Drug Delivery of MOE,School of Pharmacy,Fudan University,Shanghai 201203,China [2]Center for Medical Research and Innovation,Shanghai Pudong Hospital,Fudan University Pudong Medical Center,Shanghai 201399,China [3]Shanghai Skin Disease Hospital,Tongji University School of Medicine,Shanghai 200443,China [4]Key Laboratory for Tibet Plateau Phytochemistry of Qinghai Province,School of Pharmacy,Qinghai Nationalities University,Xining 810007,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第5期2479-2493,共15页药学学报（英文版）

基　　金：supported by the National Natural Science Foundation of China(Nos.81872815,82030107,and 81690263);Science and Technology Commission of Shanghai Municipality(No.19XD1400300,China)。

摘　　要：The long-circulating effect is revisited by simultaneous monitoring of the drug payloads and nanocarriers following intravenous administration of doxorubicin(DOX)-loaded methoxy polyethylene glycol-polycaprolactone(mPEG-PCL) nanoparticles. Comparison of the kinetic profiles of both DOX and nanocarriers verifies the long-circulating effect, though of limited degree, as a result of pegylation. The nanocarrier profiles display fast clearance from the blood despite dense PEG decoration;DOX is cleared faster than the nanocarriers. The nanocarriers circulate longer than DOX in the blood, suggesting possible leakage of DOX from the nanocarriers. Hepatic accumulation is the highest among all organs and tissues investigated, which however is reversely proportionate to blood circulation time. Pegylation and reduction in particle size prove to extend circulation of drug nanocarriers in the blood with simultaneous decrease in uptake by various organs of the mononuclear phagocytic system. It is concluded that the long-circulating effect of mPEG-PCL nanoparticles is reconfirmed by monitoring of either DOX or the nanocarriers, but the faster clearance of DOX suggests possible leakage of a fraction of the payloads. The findings of this study are of potential translational significance in design of nanocarriers towards optimization of both therapeutic and toxic effects.

关 键 词：LONG-CIRCULATING In vivo fate Aggregation-caused quenching NANOPARTICLES mPEG-PCL DOXORUBICIN Drug delivery Pharmacokinetics 

分 类 号：R943[医药卫生—药剂学]