In Vitro Evaluation of Anti-Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions

Yinan Chen, George R. Dakwar, Kevin Braeckmans, Twan Lammers, Wim E. Hennink, Josbert M. Metselaar (Corresponding Author)

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Abstract

The in vivo stability and biodegradability of nanocarriers crucially determine therapeutic efficacy as well as safety when used for drug delivery. This study aims to evaluate optimized in vitro techniques predictive for in vivo nanocarrier behavior. Polymeric biodegradable nanogels based on hydroxyethyl methacrylamide-oligoglycolates-derivatized poly(hydroxyethyl methacrylamide-co-N-(2-azidoethyl)methacrylamide) and with various degrees of PEGylation and crosslinking densities are prepared. Three techniques are chosen and refined for specific in vitro evaluation of the nanocarrier performance: (1) fluorescence single particle tracking (fSPT) to study the stability of nanogels in human plasma, (2) tangential flow filtration (TFF) to study the degradation and filtration of nanogel degradation products, and (3) fluorescence fluctuation spectroscopy (FFS) to evaluate and compare the degradation behavior of nanogels in buffer and plasma. fSPT results demonstrate that nanogels with highest PEGylation content show the least aggregation. The TFF results reveal that nanogels with higher crosslink density have slower degradation and removal by filtration. FFS results indicate a similar degradation behavior in human plasma as compared to that in phosphate buffered saline. In conclusion, three methods can be used to compare and select the optimal nanogel composition, and these methods hold potential to predict the in vivo performance of nanocarriers.

Original languageEnglish
Article number1700127
JournalMacromolecular bioscience
Volume18
Issue number1
DOIs
Publication statusPublished - 1 Jan 2018

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Agglomeration
Degradation
Fluorescence
Plasma (human)
Fluorescence Spectrometry
Spectroscopy
Biodegradability
Drug delivery
Crosslinking
Phosphates
NanoGel
In Vitro Techniques
Plasmas
Buffers
Chemical analysis
Safety
Pharmaceutical Preparations
methacrylamide

Keywords

  • UT-Hybrid-D
  • fluorescence correlation spectroscopy (FFS)
  • fluorescence single particle tracking (fSPT)
  • stability
  • tangential flow filtration (TFF)
  • degradation

Cite this

Chen, Yinan ; Dakwar, George R. ; Braeckmans, Kevin ; Lammers, Twan ; Hennink, Wim E. ; Metselaar, Josbert M. / In Vitro Evaluation of Anti-Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions. In: Macromolecular bioscience. 2018 ; Vol. 18, No. 1.
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abstract = "The in vivo stability and biodegradability of nanocarriers crucially determine therapeutic efficacy as well as safety when used for drug delivery. This study aims to evaluate optimized in vitro techniques predictive for in vivo nanocarrier behavior. Polymeric biodegradable nanogels based on hydroxyethyl methacrylamide-oligoglycolates-derivatized poly(hydroxyethyl methacrylamide-co-N-(2-azidoethyl)methacrylamide) and with various degrees of PEGylation and crosslinking densities are prepared. Three techniques are chosen and refined for specific in vitro evaluation of the nanocarrier performance: (1) fluorescence single particle tracking (fSPT) to study the stability of nanogels in human plasma, (2) tangential flow filtration (TFF) to study the degradation and filtration of nanogel degradation products, and (3) fluorescence fluctuation spectroscopy (FFS) to evaluate and compare the degradation behavior of nanogels in buffer and plasma. fSPT results demonstrate that nanogels with highest PEGylation content show the least aggregation. The TFF results reveal that nanogels with higher crosslink density have slower degradation and removal by filtration. FFS results indicate a similar degradation behavior in human plasma as compared to that in phosphate buffered saline. In conclusion, three methods can be used to compare and select the optimal nanogel composition, and these methods hold potential to predict the in vivo performance of nanocarriers.",
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In Vitro Evaluation of Anti-Aggregation and Degradation Behavior of PEGylated Polymeric Nanogels under In Vivo Like Conditions. / Chen, Yinan; Dakwar, George R.; Braeckmans, Kevin; Lammers, Twan; Hennink, Wim E.; Metselaar, Josbert M. (Corresponding Author).

In: Macromolecular bioscience, Vol. 18, No. 1, 1700127, 01.01.2018.

Research output: Contribution to journalArticleAcademicpeer-review

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