Nanostructure and Molecular-Level Characterization of Aminoalkyl Methacrylate Copolymer and the Impact on Drug Solubilization Ability,Molecular Pharmaceutics

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Nanostructure and Molecular-Level Characterization of Aminoalkyl Methacrylate Copolymer and the Impact on Drug Solubilization Ability
Molecular Pharmaceutics ( IF 4.5 ) Pub Date : 2021-10-12 , DOI: 10.1021/acs.molpharmaceut.1c00526
Yuta Okamoto ₁ , Kenjirou Higashi ₁ , Takeshi Morita ₂ , Keisuke Ueda ₁ , Sayaka Mukaide ₁ , Junpei Takeda ₃ , Masatoshi Karashima ₃ , Yukihiro Ikeda ₃ , Kunikazu Moribe ₁

Affiliation

The effects of pH changes and saccharin (SAC) addition on the nanostructure and mobility of the cationic aminoalkyl methacrylate copolymer Eudragit E PO (EUD-E) and its drug solubilization ability were investigated. Small-angle X-ray scattering performed using synchrotron radiation and atomic force microscopy showed that the EUD-E nanostructure, which has a size of approximately several nanometers, changed from a random coil structure at low pH (pH 4.0–5.0) to a partially folded structure at high pH (pH 5.5–6.5). The EUD-E also formed a partially folded structure in a wide pH range of 4.5–6.5 when SAC was present, and the coil-to-globule transition was moderate with pH increase, compared with that when SAC was absent. The equilibrium solubility of the neutral drug naringenin (NAR) was enhanced in the EUD-E solution and further increased as the pH increased. The enlargement of the hydrophobic region of EUD-E in association with the coil-to-globule transition led to efficient solubilization of NAR. The interaction with SAC enhanced the mobility of the EUD-E chains in the hydrophobic region of EUD-E, resulting in changes in the drug-solubilizing ability. ¹H high-resolution magic-angle spinning NMR measurements revealed that the solubilized NAR in the partially folded structure of EUD-E showed higher molecular mobility in the presence of SAC than in the absence of SAC. This study highlighted that solution pH and the presence of SAC significantly changed the drug solubilization ability of EUD-E, followed by changes in the EUD-E nanostructure, including its hydrophobic region.

中文翻译：

甲基丙烯酸氨基烷基酯共聚物的纳米结构和分子级表征及其对药物增溶能力的影响

研究了 pH 变化和糖精 (SAC) 添加对阳离子甲基丙烯酸氨基烷基酯共聚物 Eudragit E PO (EUD-E) 的纳米结构和迁移率及其药物增溶能力的影响。使用同步辐射和原子力显微镜进行的小角 X 射线散射表明，尺寸约为几纳米的 EUD-E 纳米结构从低 pH（pH 4.0-5.0）下的无规线圈结构变为部分在高 pH 值（pH 5.5–6.5）下的折叠结构。当存在 SAC 时，EUD-E 在 4.5-6.5 的宽 pH 范围内也形成部分折叠结构，与不存在 SAC 时相比，随着 pH 的增加，螺旋向球的转变是适度的。中性药物柚皮素 (NAR) 的平衡溶解度在 EUD-E 溶液中增强，并随着 pH 值的增加而进一步增加。EUD-E 疏水区域的扩大与线圈到球的转变相关，导致 NAR 的有效溶解。与 SAC 的相互作用增强了 EUD-E 链在 EUD-E 疏水区域的流动性，导致药物溶解能力发生变化。¹ H 高分辨率魔角旋转 NMR 测量表明，在 EUD-E 的部分折叠结构中溶解的 NAR 在存在 SAC 的情况下比在不存在 SAC 的情况下表现出更高的分子迁移率。该研究强调溶液 pH 值和 SAC 的存在显着改变了 EUD-E 的药物增溶能力，随之而来的是 EUD-E 纳米结构的变化，包括其疏水区域。

更新日期：2021-11-01

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