Abstract
Purpose :
Sheardown lab has previously developed hydrogels consisting of Poly(N-isopropylacrylamide) (PNIPAAm) [Fitzpatrick, S.D., et al., Acta Biomaterialia, 2012. 8(7)]. Compared to other implants, this PNIPAAm based gel has an advantage that it is injectable directly into the vitreous cavity in the form of a solution, where it gels in-situ at physiological temperature (37 °C) and have shown to be stable over a period of 5-8 months. This study investigates improving stability of these gels via cross-linking, evaluating these gels for rheology and long-term protein release.
Methods :
Poly(ethylene glycol) diacrylate (PEGDA) (MW: 2000) was used as a cross-linker to increase cross-linking of PNIPAAm polymer chains. This cross-linker was introduced during the free-radical polymerization process and the successful cross-linking was confirmed by NMR. The hydrogel was prepared using a 10%, 12.5% and 15% polymer solution (w/v) heated to 37 °C. These hydrogels were characterized for their injectability using a 30 G needle. Rheology studies were performed using a Pelltier plate on a Discovery Hybrid Rheometer at 37 °C. For in-vitro drug release studies, IgG protein was dissolved in the hydrogel solution at room temperature. The drug containing hydrogel solution was then injected into the PBS kept in a water bath at 37 °C. Samples were collected periodically and analyzed on a plate-reader after treating with the Bradford reagent.
Results :
NMR confirmed the successful cross-linking of the PNIPAAm polymer chains. Injectability studies showed that polymer solution of 12.5% (w/v) could be injected via a 30 G needle; whereas 15% (w/v) solution caused the needle to pop-out during the injection process. Rheology studies revealed that higher cross-linking improves viscosity and stability which is desired for a long-term protein release drug delivery system. For in-vitro drug release, 12.5% (w/v) PNIPAAm was selected as this would later translate into in-vivo studies using a 30 G needle. In-vitro drug release study showed a burst release during the first 24 hours (~20%); however, a sustained release pattern was observed thereafter with a total of 40% drug release in first four weeks.
Conclusions :
Highly cross-linked and more stable but still injectable PNIPAAm hydrogel was prepared successfully. In-vitro drug release data showed a sustained release pattern which is highly desirable for the long-term treatment of chronic conditions affecting retina.
This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.