Water-soluble and amphiphilic phospholipid
copolymers having 2-methacryloyloxyethyl
phosphorylcholine units for the solubilization of
bioactive compounds

We summarize the development and evaluation of new type of phospholipid polymers as a solubilizer for poorly water-soluble compounds. That is, a water-soluble and amphiphilic poly(2-methacryloyloxyethyl phosphorylcholine-random-n-butyl methacrylate) contains 30 mol% hydrophilic 2-methacryloyloxyethyl phosphorylcholine units and its weight-averaged molecular weight is around 5.0 × 104 .When the polymer is dissolved in an aqueous medium, a large portion of hydrophobic n-butyl methacrylate units assemble, forming polymer aggregates. To avoid severe biological reactions caused by conventional solubilizers, the phospholipid polymer can be applied for the solubilization of poorly water-soluble bioactive compounds. The polarity inside these polymer aggregate is the same as that of ethanol and n-butanol. Therefore, bioactive compounds, whose solubility is poor in water but good in these alcohols, can be entrapped in the polymer aggregate. The phospholipid polymer can penetrate the cell membrane by molecular diffusion, carrying inside the cell the bioactive compound, without exhibiting significant cytotoxicity. Several animal experiments have revealed that the pharmacological performance of various bioactive compound/phospholipid polymer complexes is excellent. Furthermore,functionalization of the polymer aggregate with biomolecules, such as antibodies and oligonucleotides, can be done, leading to selective capturing of the target molecules. These examples clearly indicate that water-soluble and amphiphilic phospholipid polymer is a candidate for preparing safer formulations and more effective pharmaceutical treatment with several bioactive compounds.

Poly(MPC-random-BMA) (PMB) is a typical water-soluble and amphiphilic MPC copolymer, whose weight-averaged molecular weight (Mw) is less than 5.0 × 104, and which is composed of 30 mol% MPC units in the polymer. The fact that 30 mol% MPC units in the polymer is enough to result in high water solubility of the relatively low Mw PMB,which contains hydrophobic BMA units, is a remarkable property of the MPC unit, since other hydrophilic methacrylate units, including carboxylate, sulfonate, and trimethylammonium groups, cannot provide enough solubility in water when the resulting polymers contain 70 mol% BMA units.

PMB is one of the candidate solubilizers for poorly water-soluble bioactive compounds administered orally or through the bloodstream. Water-soluble PMB of two different MWs is commercially available worldwide as PUREBRIGHT® from NOF Co. Ltd,Tokyo, Japan, as a solubilizing test kit for bioactive compounds. Moreover, many animal studies have revealed that PMB has a good potential to be used as a new solubilizer. We hope that the application of water-soluble and amphiphilic PMB will realize safer and more effective pharmaceutical treatment in the future. (Journal of Biomaterials Science, Polymer Edition, DOI: 10.1080/09205063.2017.1377023)