Abstract:
This study investigates the nanoscale self-assembly from mixtures of two symmetrical poly(ethylene oxide)-poly(propylene oxide)-pol(ethylene oxide) (PEO-PPO-PEO) block copolymers (BCPs) with different lengths of PEO blocks and similar PPO blocks. The blended BCPs (commercially known as Pluronic F88 and L81, with 80 and 10% PEO, respectively) exhibited rich phase behavior in an aqueous solution. The relative viscosity (ηrel) indicated significant variations in the flow behavior, ranging from fluidic to viscous, thereby suggesting a possible micellar growth or morphological transition. The tensiometric experiments provided insight into the intermolecular hydrophobic interactions at the liquid-air interface favoring the surface activity of mixed-system micellization. Dynamic light scattering (DLS) and small-angle neutron scattering (SANS) revealed the varied structural morphologies of these core-shell mixed micelles and polymersomes formed under different conditions. At a concentration of ≤5% w/v, Pluronic F88 exists as molecularly dissolved unimers or Gaussian chains. However, the addition of the very hydrophobic Pluronic L81, even at a much lower (<0.2%) concentration, induced micellization and promoted micellar growth/transition. These results were further substantiated through molecular dynamics (MD) simulations, employing a readily transferable coarse-grained (CG) molecular model grounded in the MARTINI force field with density and solvent-accessible surface area (SASA) profiles. These findings proved that F88 underwent micellar growth/transition in the presence of L81. Furthermore, the potential use of these Pluronic mixed micelles as nanocarriers for the anticancer drug quercetin (QCT) was explored. The spectral analysis provided insight into the enhanced solubility of QCT through the assessment of the standard free energy of solubilization (ΔG°), drug-loading efficiency (DL%), encapsulation efficiency (EE%), and partition coefficient (P). A detailed optimization of the drug release kinetics was presented by employing various kinetic models. The [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] MTT assay, a frequently used technique for assessing cytotoxicity in anticancer research, was used to gauge the effectiveness of these QCT-loaded mixed nanoaggregates.
摘要:
本研究调查了两种对称的聚(环氧乙烷)-聚(环氧丙烷)-聚(环氧乙烷)(PEO-PPO-PEO)嵌段共聚物(BCP)的混合物的纳米级自组装,它们具有不同长度的PEO嵌段和相似的PPO嵌段。混合的BCP(商业上称为PluronicF88和L81,具有80%和10%的PEO,分别)在水溶液中表现出丰富的相行为。相对粘度(ηrel)表明流动行为的显着变化,从流体到粘性,从而表明可能的胶束生长或形态转变。张力计实验提供了对液-气界面处分子间疏水相互作用的深入了解,有利于混合体系胶束化的表面活性。动态光散射(DLS)和小角度中子散射(SANS)揭示了在不同条件下形成的这些核壳混合胶束和聚合物囊泡的不同结构形态。在≤5%w/v的浓度下,PluronicF88作为分子溶解的unimer或高斯链存在。然而,添加非常疏水的PluronicL81,即使在更低(<0.2%)的浓度下,诱导胶束化并促进胶束生长/过渡。这些结果通过分子动力学(MD)模拟得到进一步证实,采用易于转移的粗粒(CG)分子模型,在具有密度和溶剂可及表面积(SASA)分布的MARTINI力场中接地。这些发现证明F88在L81存在下经历胶束生长/转变。此外,探索了这些Pluronic混合胶束作为抗癌药物槲皮素(QCT)纳米载体的潜在用途。通过评估标准的溶解自由能(ΔG°),光谱分析提供了对QCT溶解度增强的见解。载药率(DL%),封装效率(EE%),和分配系数(P)。通过采用各种动力学模型,对药物释放动力学进行了详细的优化。[3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴化物]MTT测定,一种在抗癌研究中经常使用的评估细胞毒性的技术,用于测量这些QCT负载的混合纳米聚集体的有效性。