Lee Chin-Fen, Yang Ching-Hsun, Lin Tsang-Lang, Bahadur Pratap, Chen Li-Jen
Department of Chemical Engineering, National Taiwan University, Taipei, 10617, Taiwan.
Department of Engineering and System Science, National Tsing Hua University, Hsinchu, 30013, Taiwan.
Colloids Surf B Biointerfaces. 2019 Nov 1;183:110461. doi: 10.1016/j.colsurfb.2019.110461. Epub 2019 Aug 26.
The binary P123 + F108, + F98, + F88, + F68, + F87 and + P84 systems were used to systematically explore the effect of molecular weight and hydrophobicity of Pluronic on the tendency of cooperative binding between parent copolymers and solubility of drug (ibuprofen) in these mixed Pluronic systems. Temperature-dependent co-micellization process in these systems was carefully investigated by using high sensitivity differential scanning calorimeter (HSDSC), dynamic light scattering (DLS) and small angle X-ray scattering (SAXS). All the HSDSC thermograms for these systems consistently exhibit two endothermic (micellization) peaks apart by at least 13.3 °C. It was evidenced that micelles are mainly formed by P123, the copolymer with a lower critical micelle temperature (CMT), at low temperatures. Raising temperature would dehydrate the other Pluronic with a higher CMT to be integrated into the neat P123 micelles developed at low temperatures. When the temperature is further increased beyond the second endothermic peak, the mixed micelles with a two-shell structure and characteristic corona lengths of their parent copolymers are observed to prove the existence of cooperative binding between parent copolymers. All the binary mixed Pluronic systems used in this study exhibit cooperative binding to form unimodal distribution of mixed micelles, except the P123 + F68 system. The SAXS results show that P123 + F68 system at 65 °C exhibits bimodal distribution of aggregates with coexisting of neat F68 micelles (65% in number) and P123 + F68 mixed micelles (35% in number). It is interesting to find out that P123 and F68 with distinct polypropylene oxide (PPO) moieties (i.e., a difference of 37 PO units) would exhibit very weak cooperative binding to partially form mixed micelles. Addition of ibuprofen in the P123 + F68 system would substantially enhance the cooperative binding between P123 and F68 to form bimodal distribution of aggregates with coexisting of neat F68 micelles (drops down to 30% in number) and P123 + F68 mixed micelles (increases up to 70% in number). For the systems with ibuprofen incorporated, SAXS results demonstrate that the drug is mainly encapsulated in the core of neat micelles developed at low temperatures. The solubility of ibuprofen in the 0.5 wt% P123 + 0.368 wt% P84 system is as high as 2.62 mg/ml, which is 114 times more than that in pure water at 37 °C.
采用二元P123+F108、+F98、+F88、+F68、+F87和+P84体系，系统地研究了泊洛沙姆的分子量和疏水性对母体共聚物之间协同结合趋势以及药物（布洛芬）在这些混合泊洛沙姆体系中溶解度的影响。利用高灵敏度差示扫描量热仪（HSDSC）、动态光散射（DLS）和小角X射线散射（SAXS），仔细研究了这些体系中随温度变化的共胶束化过程。这些体系的所有HSDSC热谱图均一致显示出两个吸热（胶束化）峰，其间隔至少为13.3°C。有证据表明，在低温下，胶束主要由临界胶束温度（CMT）较低的共聚物P123形成。升高温度会使另一种CMT较高的泊洛沙姆脱水，从而整合到低温下形成的纯P123胶束中。当温度进一步升高超过第二个吸热峰时，观察到具有双亲共聚物特征冠层长度的双壳结构混合胶束，证明了双亲共聚物之间存在协同结合。本研究中使用的所有二元混合泊洛沙姆体系均表现出协同结合，形成混合胶束的单峰分布，但P123+F68体系除外。SAXS结果表明，65°C下的P123+F68体系表现出聚集体的双峰分布，其中纯F68胶束（数量占65%）和P123+F68混合胶束（数量占35%）共存。有趣的是，具有不同聚环氧丙烷（PPO）部分（即相差37个PO单元）的P123和F68表现出非常弱的协同结合，只能部分形成混合胶束。在P123+F68体系中加入布洛芬将显著增强P123和F68之间的协同结合，形成聚集体的双峰分布，其中纯F68胶束（数量降至30%）和P123+F68混合胶束（数量增至70%）共存。对于加入布洛芬的体系，SAXS结果表明，药物主要包裹在低温下形成的纯胶束的核心中。布洛芬在0.5 wt% P123+0.368 wt% P84体系中的溶解度高达2.62 mg/ml，是其在37°C纯水中溶解度的114倍。
