Osteoclast-mediated bone loss disorders are chronically treated with bisphosphonates (BPs). Their structural similarity with inorganic pyrophosphate renders them very high affinity for bone tissue. Recently, they have shown potential antitumor activity. However, BPs suffer from several drawbacks such as polymorphism and low bioavailability which are related with the common side effects (e.g. muscle, joint and bone pain, numbness) associated with these drugs. Thus, there is a need to develop new ways to increase BPs’ bioavailability while reducing systemic toxicity.

Active Principle Ingredients as Organic Salts and Ionic Liquids (API-OSILs) has been one of the focus of our group over the last years. The combination of drugs as anions or cations with biocompatible organic counter ions has proven to be an innovative approach to tackle drug polymorphism as well as to improve water solubility, permeability and corresponding bioavailability and biological activity.

In this communication, we report the preparation of anionic etidronate, alendronate and zoledronate-based BP-OSILs in quantitative yields. The polymorphic profile of the prepared BP-OSILs and their solubility in water and biological fluids, as well as toxicity towards human healthy and lung, breast and bone cancer cell lines will be presented. Finally, the effect of etidronate-OSILs on osteoblast- and osteoclastogenesis will also be disclosed.