Drug-Releasing Thermogel for Osteoarthritis Induction in an Animal Model

The induction of disease states in animal models is an essential step in new drug discovery procedures. In this study, osteoarthritis (OA) was induced in a mouse model using a polypeptide thermogel-based sustained drug release system. Hydrophilic lactobionic acids and hydrophobic n-butyric acids were grafted onto epsilon-poly-(l-lysine) to prepare a thermogelling polymer of epsilon-poly-(l-lysine) grafted with lactobionic acid and butyric acid (PLLB). The gel modulus of PLLB is about 1000 Pa at 37 C-degrees. Collagenase, which causes OA, was slowly released from the PLLB thermogel over two weeks. The PLLB formulation containing collagenases ranging from 1-10 units was intra-articularly injected into the knee of mice. OA mouse models with Osteoarthritis Research Society International (OARSI) grades of 3-6 were developed depending on the amounts of collagenase incorporated in the PLLB thermogel formulation. This study suggests that thermogel-based drug release formulations can be a precise tool for developing animal disease models in a dose-dependent manner.