Accelerated Blood Clearance of PEGylated PLGA Nanoparticles Following Repeated Injections: Effects of Polymer Dose, PEG Coating, and Encapsulated Anticancer Drug

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• 作者：Roonak Saadati (1)
  Simin Dadashzadeh (1) (2)
  Zahra Abbasian (1)
  Hoorieh Soleimanjahi (3)
  
• 关键词：accelerated blood clearance (ABC) ; anti ; PEG IgM antibody ; etoposide ; pharmacokinetics ; PLGA ; PEG nanoparticles
• 刊名：Pharmaceutical Research
• 出版年：2013
• 出版时间：April 2013
• 年：2013
• 卷：30
• 期：4
• 页码：985-995
• 全文大小：377KB
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• 作者单位：Roonak Saadati (1)
  Simin Dadashzadeh (1) (2)
  Zahra Abbasian (1)
  Hoorieh Soleimanjahi (3)
  
  1. Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University of Medical Sciences, PO Box 14155-153, Tehran, Iran
  2. Pharmaceutical Sciences Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  3. Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
  
• ISSN：1573-904X

文摘

Purpose To investigate accelerated blood clearance (ABC) induction upon repeated injections of PLGA-PEG nanoparticles as a commonly used polymeric drug carrier. Methods Etoposide-loaded PLGA-PEG NPs were developed and administered as the test dose to rats pre-injected with various NP treatments at certain time intervals. Pharmacokinetic parameters of etoposide and production of anti-PEG IgM antibody were evaluated. Results A notable ABC effect was induced by a wide range of polymer doses (0.1 to 20?mg) of empty NPs, accompanied by IgM secretion. However, a further increase in polymer dose resulted not only in the abrogation of the observed ABC induction but also in distinctly a higher value for AUC of the NPs relative to the control. The data from the PEG-negative group verified the fundamental role of PEG for ABC induction. The first injection of etoposide-containing PEGylated nanoparticles (a cell cycle phase-specific drug) produced a strong ABC phenomenon. Three sequential administrations of etoposide-loaded NPs abolished ABC, although a high level of IgM was still detected, which suggests saturation with insignificant poisoning of immune cells. Conclusion The presented results demonstrate the importance of clinical evaluations for PLGA-PEG nanocarriers that consider the administration schedule in multiple drug delivery, particularly in cancer chemotherapy.