A Thixotropic Polyglycerol Sebacate-Based Supramolecular Hydrogel as an Injectable Drug Delivery Matrix

Abstract

We have developed a “self-healing” polyglycerol sebacate—polyethylene glycol methyl ether methacrylate (PGS-PEGMEMA)/α-Cyclodextrin (αCD) hydrogel which could be sheared into a liquid during injection and has the potential to quickly “heal” itself back into gel post-injection. This hydrogel was shown to be biocompatible and biodegradable and therefore appropriate for use in vivo. Furthermore, the storage and loss moduli of the hydrogels could be tuned (by varying the concentration of αCD) between a fraction of a kPa to a few 100 kPa, a range that coincides with the moduli of cells and human soft tissues. This property would allow for this hydrogel to be used in vivo with maximal mechanical compatibility with human soft tissues. In vitro experiments showed that the hydrogel demonstrated a linear mass erosion profile and a biphasic drug (doxorubicin) release profile: Phase I was primarily driven by diffusion and Phase II was driven by hydrogel erosion. The diffusion mechanism was modeled with the First Order equation and the erosion mechanism with the Hopfenberg equation. This established fitting model could be used to predict releases with other drugs and estimate the composition of the hydrogel required to achieve a desired release rate.

Keywords

• polyglycerol sebacate
• shear-thinning
• self-healing
• injectable hydrogel
• supramolecular