Research Project
2417025
Design of new efficient drug delivery systems for proteins is one of the major themes of modern biotechnology and biopharmaceutical industry. The ideal formulation must be stable under storage, in low pH, against proteolysis, be prepared in high yield and have high protein load. We have found that ross-lined enzyme crystals (CLECsR) meet all these criteria. CLECs, however, are not very active against high molecular weight cus\strates such as proteins. We have also found that the major source of stability of CLECs is their crystallinity. In this Phase I study, we proposed a novel protein delivery system based on Stabilized Protein Crystals (SPC). We will prepare SPC of Candida rugosa lipase (CRL) that will be stable at elevated temperature (40C), low pH (2-4) and in the presence of protease, but can desolve with full release of activity when the environment conditions change. This target was chosen to address the problems of current therapies of Pancreatic Insufficiency, namely a rapid, irreversible inactivation of lipase by acid and proteases. We propose a crystalline micropartiulate fungal lipase therapeutic, stable to gastric pH and bioavailable in the duodenum. If successful, these approaches will lead not only to the development of novel lipase delivery systems for treatment of pancreatic insufficiency, but also to the introduction of novel efficient protein delivery vehicles in general.
