使用具有不同分子结构的两亲性磷脂聚合物增溶疏水性化合物。

Solubilization of poorly water-soluble compounds using amphiphilic phospholipid polymers with different molecular architectures.

机构信息

Department of Bioengineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

Department of Materials Engineering, School of Engineering, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8656, Japan.

出版信息

Colloids Surf B Biointerfaces. 2017 Oct 1;158:249-256. doi: 10.1016/j.colsurfb.2017.06.040. Epub 2017 Jun 29.

DOI:10.1016/j.colsurfb.2017.06.040

PMID:28700969

Abstract

To achieve stable and effective solubilization of poorly water-soluble bioactive compounds, water-soluble and amphiphilic polymers composed of hydrophilic 2-methacryloyloxyethyl phosphorylcholine (MPC) units and hydrophobic n-butyl methacrylate (BMA) units were prepared. MPC polymers having different molecular architectures, such as random-type monomer unit sequences and block-type sequences, formed polymer aggregates when they were dissolved in aqueous media. The structure of the random-type polymer aggregate was loose and flexible. On the other hand, the block-type polymer formed polymeric micelles, which were composed of very stable hydrophobic poly(BMA) cores and hydrophilic poly(MPC) shells. The solubilization of a poorly water-soluble bioactive compound, paclitaxel (PTX), in the polymer aggregates was observed, however, solubilizing efficiency and stability were strongly depended on the polymer architecture; in other words, PTX stayed in the poly(BMA) core of the polymer micelle formed by the block-type polymer even when plasma protein was present in the aqueous medium. On the other hand, when the random-type polymer was used, PTX was transferred from the polymer aggregate to the protein. We conclude that water-soluble and amphiphilic MPC polymers are good candidates as solubilizers for poorly water-soluble bioactive compounds.

摘要

为了实现对疏水性生物活性化合物的稳定、有效增溶，制备了由亲水性 2-甲基丙烯酰氧乙基磷酸胆碱（MPC）单元和疏水性正丁基甲基丙烯酸酯（BMA）单元组成的水溶性和两亲性聚合物。当溶解在水介质中时，具有不同分子结构的 MPC 聚合物，如无规型单体单元序列和嵌段型序列，形成聚合物聚集体。无规型聚合物聚集体的结构松散且灵活。另一方面，嵌段型聚合物形成聚合物胶束，其由非常稳定的疏水聚（BMA）核和亲水聚（MPC）壳组成。观察到疏水性生物活性化合物紫杉醇（PTX）在聚合物聚集体中的增溶，但增溶效率和稳定性强烈依赖于聚合物结构；换句话说，即使在水介质中存在血浆蛋白，PTX 也留在由嵌段型聚合物形成的聚合物胶束的聚（BMA）核中。另一方面，当使用无规型聚合物时，PTX 从聚合物聚集体转移到蛋白质上。我们得出结论，水溶性和两亲性 MPC 聚合物是疏水性生物活性化合物的良好增溶剂候选物。