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

• Published in: Macromolecular bioscience 2018-01, Vol.18 (1), p.n/a
• Main Authors: Chen, Yinan, Dakwar, George R., Braeckmans, Kevin, Lammers, Twan, Hennink, Wim E., Metselaar, Josbert M.
• Format: Article
• Language: English
• Subjects: Agglomeration; Aggregation behavior; Biodegradability; Biodegradable Plastics - chemistry; Biodegradable Plastics - pharmacology; Biodegradation; Blood plasma; Buffers; Cell Survival - drug effects; Crosslinking; Degradation; Degradation products; Drug Carriers - chemistry; Drug Carriers - pharmacology; Drug delivery; Drug Delivery Systems; Evaluation; Filtration; Flow stability; Fluorescence; fluorescence correlation spectroscopy (FFS); fluorescence single particle tracking (fSPT); Human behavior; Humans; In vitro methods and tests; In vivo methods and tests; Methacrylamide; Nanoparticles - chemistry; Nanoparticles - therapeutic use; Particle tracking; Phosphates; Plasma - drug effects; Polyethylene Glycols - chemistry; Polyethylene Glycols - pharmacology; Polyethylene Glycols - therapeutic use; Polyethyleneimine - chemistry; Polyethyleneimine - pharmacology; Polyethyleneimine - therapeutic use; Polymers - chemistry; Polymers - pharmacology; Polymers - therapeutic use; Spectrometry, Fluorescence; Spectroscopy; stability; tangential flow filtration (TFF); Variations
• ISSN: 1616-5187; 1616-5195
• DOI: 10.1002/mabi.201700127

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. Fluorescence single particle tracking, tangential flow filtration, and fluorescence fluctuation spectroscopy are developed and optimized to study the stability and degradation of polymeric nanogels with various degrees of PEGylation and crosslinking densities. They are valuable in vitro strategies to predict the in vivo behavior of nanocarriers prior to animal studies.