In vitro characteristics of a gelling PEGDA-QT polymer system with model drug release for cerebral aneurysm embolization.

Abstract

A liquid-to-solid gelling polymer system, such as the poly(ethylene glycol) diacrylate-pentaerythritol tetrakis (3-mercaptopropionate) (PEGDA-QT) system, can fill cerebral aneurysms more completely than current embolization materials, reducing the likelihood of aneurysm recurrence. PEGDA-QT gels were formulated using PEGDA of different molecular weights (PEGDA575 and PEGDA700), and their characteristics were examined in vitro. Experiments examined gel time, mass change, crosslink integrity, cytotoxicity, and protein release capabilities. In general, PEGDA575-QT gels were more hydrophobic, requiring an initiating solution with a higher pH (pH 9.5) to achieve a gel time comparable to PEGDA700-QT gels, which used an initiating solution at pH 9.19. The mass change and crosslink integrity of gels were analyzed over time after gels were submerged in 150 mM phosphate buffered saline. After 380 days, PEGDA575-QT gels achieved a maximum mass increase of 72% due to water uptake, while PEGDA700-QT gels doubled their initial mass (100% increase) by 165 days. Compression tests showed that PEGDA700-QT gels hydrolyzed more quickly than PEGDA575-QT gels. Cytotoxicity assays showed that in general, PEGDA575-QT negatively affected cell growth, while PEGDA700-QT gels promoted cell viability. Sustained, controlled release of lysozyme, a 14.3 kDa protein, was achieved over an 8-week period when loaded into PEGDA700-QT gels, but PEGDA575-QT gels did not show sustained release. These studies show that although they are similar in composition, these PEGDA-QT gel formulations behave considerably differently. Although PEGDA700-QT gels swell more and degrade faster than PEGDA575-QT gels, their cytocompatibility and protein release characteristics may prove to be more beneficial for in vivo aneurysm treatment.

• Authors: Kristen F Soodak, Celeste R Brennecka, Brent L Vernon
• Journal: Journal of biomedical materials research. Part B, Applied biomaterials (J Biomed Mater Res B Appl Biomater) Vol. 101 Issue 8 Pg. 1477-88 (Nov 2013) ISSN: 1552-4981 [Electronic] United States
• PMID: 24591225 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Wiley Periodicals, Inc.

Chemical References

• Cross-Linking Reagents
• Polymers
• poly(ethylene glycol) diacrylate-pentaerythritol tetrakis(3-mercaptopropionate)
• poly(ethylene glycol)diacrylate
• Water
• Polyethylene Glycols
• 3-Mercaptopropionic Acid
• Muramidase

Topics

• 3-Mercaptopropionic Acid (analogs & derivatives, chemistry)
• 3T3 Cells
• Animals
• Compressive Strength
• Cross-Linking Reagents (chemistry)
• Drug Delivery Systems
• Embolization, Therapeutic (methods)
• Hydrogen-Ion Concentration
• Intracranial Aneurysm (drug therapy)
• Kinetics
• Materials Testing
• Mice
• Molecular Weight
• Muramidase (chemistry)
• Polyethylene Glycols (chemistry)
• Polymers (chemistry)
• Rheology
• Water (chemistry)