Controlled crystalline based drug delivery systems for long-term therapies

Medical implants and controlled drug delivery systems have revolutionized modern medicine and life quality for millions of patients worldwide. However, following their insertion immune-mediated foreign body response (FBR) is anticipated to the materials of these devices/delivery systems, which can significantly limit their function or even induce failure. This work describe the development and validation of an extremely long-term and controlled-release formulations based crystalized drug formulation for local anti-inflammatory release. These formulations are based solvent-free and compact crystals. As such giving the engineered compact crystalline lattice structure, these crystals allows for high drug density as well as very slow surface dissolution (i.e. Layer-by-Layer mechanism). These formulations were found to suppress FBR in both rodents and non-human primates for at least 1.3 years and 6 months, respectively. These formulations were found to inhibit FBR across multiple implant sites— intramuscular, intraperitoneal and subcutaneous. Also these formulations were tested into a range of devices, including human islet microencapsulation systems, muscle-stimulating devices and electrode-based continuous glucose-sensing monitors (CGMs), and found to inhibits fibrosis, thereby allowing for extended function. Also, in this work few examples of engineered medicinal polymers with bioactive functional moieties in their polymeric backbone will be presented and their functional moieties design will be elaborated for preventing fibrosis. We strongly believe that both local, long-term crystalline based controlled release and polymeric functionalization can enhances and extends function in a range of medical devices as well as provides a generalized solution to the local immune response to implanted biomaterials and delivery systems.