Solubilization of Poorly Water-soluble Drugs with Amphiphilic Phospholipid Polymers

Most drug candidates developed in recent years are poorly water-soluble, which is a key challenge in pharmaceutical science. Various solubilization methods have been investigated thus far, most of which require solubilizers that provide a local hydrophobic environment wherein a drug can dissolve or induce interactions with drug molecules. We have focused on amphiphilic 2-methacryloyloxyethyl phosphoryl choline (MPC) polymers. In addition to the ease of molecular design of amphiphilic MPC polymers owing to their chemical structures, they have been reported to possess high biocompatibility in various biomaterial applications. Additionally, amphiphilic MPC polymers have been applied in the pharmaceutical field, especially in solubilization. We have qualitatively and quantitatively evaluated the effects of the chemical structure and physical properties of the solubilizer on the MPC polymers. In particular, MPC polymers with different chemical structures were designed and synthesized. The inner polarity and molecular mobility in the polymer aggregates were evaluated, indicating that the intrinsic properties reflect the chemical structure of the polymer. Additionally, amphiphilic MPC polymers were used to improve the solubility of poorly water-soluble drugs and as solid dispersion carriers, and they exhibited superior solubilizing abilities compared to a commonly used polymer. Furthermore, the solubility of biopharmaceuticals, such as peptides, was improved. It is possible to design and synthesize optimal structures based on the polarity of the hydrophobic environment and the intermolecular interaction with a drug. This research provides a unified interpretation of drugs and efficiently summarizes knowledge about drug development, which will facilitate the efficient and rapid development of drug formulations.