SYNTHESIS AND CHARACTERIZATION OF AN IN SITU FORMING HYDROGEL FOR USE AS A VITREOUS SUBSTITUTE

Abstract

 

Purpose

 

We have previously shown that thiol containing acrylamide co-polymers can gel in situ, and have been compatible in rabbit eyes (Swindle, KB IOVS 2008). We have seen a need for inhibiting cellular attachment and proliferation to prevent cell traction and potential for Proliferative Vitreoretiopathy (PVR). Acrylamide-phosphocholine (APC), as a known anti-proliferative agent, was added to the acrylamide co-polymer to address the problem. With the addition of the component APC, we believe this new formulation has the potential to form a hydrogel in-situ through thiol oxidation capable of preventing retinal tractional detachment.

 

Methods

 

Co-polymers were synthesized according to an established protocol for an acrylamide/acrylic acid copolymer (Aliyar, AH 2005). APC was added in mole percent varying from 0-7.5%. The co-polymer, which includes APC, was characterized by gas permeation chromatography (GPC), nuclear magnetic resonance (NMR), thiol content, and rheology. Thiol content was determined by H¹ NMR and Ellman’s reagent independently.

 

Results

 

The presence/absence of 20% acrylic acid did not affect the GPC results. Number average molecular weight was 314 kDa without and 313 kDa with acrylic acid (polydispersity of 1.79 and 2.09 respectively). Thiol content was tested by Ellman’s reagent and showed a concentration of -SH groups at 4.11 x 10-4 molSH/g, which is 65% of theoretical which is lower than the level found in similar co-polymer without APC. With the addition of the APC, the polymer was able to gel at a 1.25% w/w concentration at a modulus greater than that of a 2.0% concentration without the APC (Fig. 1).

 

Conclusions

 

We successfully incorporated APC into our previously established co-polymer. We believe we have found a uniquely suitable formulation for an in-situ gelling hydrogel which can be used as a reversible vitreous substitute. A vitreous substitute with the ability to tamponade the retina while inhibiting cell traction will reduce recovery time after vitrectomy and lower the likelihood of future procedures by inhibiting PVR.

 

 

Figure 1: Frequency scan with 5% shear strain showing storage modulus of acrylamide regelled acrylamide co-polymer with the addition of APC (blue) and without APC (red).

 

Keywords: 764 vitreous substitutes