Engineering of Crystalline-Based Formulations for Controlled Release of Antifibrotic Drugs for Long- term Therapies and Complexed Implants Rejection Prevention Applications

Medical implants are revolutionizing therapeutics and impacting the lives of hundreds of millions of patients worldwide. However, following their insertion they are subject to a host immune response that may lead to a reduction in the treatment effectiveness up to implant failure. A well-known attempt to overcome this limitation is by the administration of anti-inflammatory drugs to mitigate host response and enhance the stability and functionality of the implants[1]. This is more challenging for higher immunogenic implants, e.g., cell-based therapeutics, such as the case for encapsulated β-cells for curing type-1-diabetes. While short-term systemic delivery of anti-fibrotic drugs can temporarily inhibit the recruitment of inflammatory cells, long-term systemic administration of immune suppressants resulted in a long list of deleterious side effects including nephrotoxicity. Alternatively, a few studies have suggested that the localized release of immunomodulating agents reduces host response to the implant. In most of these cases, a polymeric carrier is applied with the drug and that is by itself has to be biocompatible as well as responsible for drug release kinetics and stability. A polymer that fully answers those requirements remains a challenge [2]. Alternatively, this work offers engineering single [3] and advanced crystalline formulation of anti inflammatory and macrophages specific targeting agents that can be slowly released and for a long-term scale of several months to years.